Abstract
Aims/Introduction
To examine the association between diabetes and prediabetes at baseline, and disability, mortality over a 22‐year period among middle‐aged Japanese adults.
Materials and Methods
Participants consisted of 1,788 adults aged 45–64 years at baseline from the cohort study National Integrated Project for Prospective Observation of Non‐communicable Disease and its Trends in the Aged 1990 (NIPPON DATA90). Disability, defined as having a decline in activities of daily living (ADL), was assessed by a modified Katz questionnaire at four time points. Disability and death without disability for 22‐year follow up were used as outcomes to test the association with a diagnosis of diabetes or prediabetes at baseline, using multinomial logistic regression. Adjusted odds ratios (ORs) were obtained from four models that contained appropriate adjustment factors, such as age, sex, smoking status, drinking status, body mass index and cardiovascular risk factors (hypertension, hypercholesterolemia, triglycerides, low serum high‐density lipoprotein), at baseline.
Results
In the present study, 334 participants (18.7%) reported at least one disability, and 350 (19.6%) were reported dead without observation of disability during follow up. Adjusting sex and other risk factors, participants with diabetes and prediabetes had a higher risk for disability (OR 1.43, 95% confidence interval [CI] 1.07–1.91 and OR 1.66, 95% CI 1.10–2.50, respectively) and for mortality (OR 1.56, 95% CI 1.16–2.08 and OR 1.77, 95% CI 1.18–2.65, respectively) than individuals with normal glucose tolerance.
Conclusions
In middle‐aged Japanese adults, individuals with diabetes and prediabetes were more likely to be associated with disability and mortality. Our findings suggest that prediabetes and diabetes in middle‐aged adults should be paid more attention, and requires more intervention to prevent disability and mortality in later life.
Keywords: Disability, Mortality, Prediabetes
The development of disability and mortality in later life among middle‐age adults Japanese with prediabetes and diabetes is unknown. Our study has long term follow up and repeatedly measured the interest outcome, which overcoming the limitations of previous published studies.
INTRODUCTION
Diabetes is a global public health issue, which is increasing rapidly in incidence and prevalence 1 . The rise of diabetes in Asia is surpassing earlier predictions, and poses huge social and economic problems to most nations in the region, and could impede national and global development. In Japan, diabetes is one of the major causes of death and disability, accounting for 11.2% nationwide 2 . Increases in the number of people with diabetes requiring dialysis might place a great burden on Japan's social security system 3 .
Diabetes and its complications could lead to severe damage to the heart, eyes, kidneys and nervous system, which diminishes the patient's quality of life 4 , 5 . Disability, defined as a decline in activities of daily living (ADL), is considered as a long‐term effect of diabetes on general health 6 , 7 , 8 . Wong et al. 9 reported that people with diabetes had 51–82% higher mobility disability and ADL decline than people without diabetes. A recent study in the USA found that middle‐aged adults with diabetes experienced disability onset 6–7 years earlier than those without diabetes 10 . Prediabetes was associated with an increased risk of all‐cause mortality, faster deterioration in chair stand performance, slower walking speed and disability than people with normal glucose tolerance 11 , 12 . However, most of the past studies were carried out on elderly populations with a cross‐sectional design, self‐reported diagnosis for diabetes, and only focused on the overall effect of diabetes and comorbidities on disability 13 , 14 . Thus, the association of prediabetes with disability and death without disability among middle‐aged adults remains uncertain. If prediabetes among middle‐aged adults is associated with future risk of disability and mortality, the findings would support the evidence to recommend early lifestyle modification in the prediabetes stage, which might be easier to control than in diabetes.
In the present study, we carried out a longitudinal analysis using a Japanese cohort study of national representatives to examine the association of diabetes and prediabetes among middle‐aged Japanese adults at baseline in 1990 with two outcomes of interest in later life, including disability and death without disability at 22‐year follow up.
MATERIALS AND METHODS
Study population
The National Integrated Project for Prospective Observation of Non‐communicable Disease and its Trends in the Aged 1990 (NIPPON DATA90) was a cohort study. The baseline survey was carried out in 1990 as the National Survey on Circulatory Disorders. A total of 8,383 community residents (3,503 men, 4,880 women; aged ≥30 years) from 300 randomly selected areas participated in the survey, with a participation rate of 76.5% (8,383 of 10,956). NIPPON DATA90 also conducted a survey of ADL for participants aged 65 years and older in 1995 15 , 16 , 17 , 18 . The ethics committee of Shiga University of Medical Science approved this study. In the present study, we excluded those who met the following criteria: 4,690 participants who were aged <45 years and aged ≥65 years in 1990 (i.e., baseline), 47 participants who had a history of stroke in 1990, 272 participants with missing baseline data, and 1,586 participants who were lost to follow up or had no record of living status nor any ADL investigation in the 22‐year follow up. Thus, 1,788 were eligible for the analysis (Figure 1).
Figure 1.
Study cohort creation. A total of 8,383 community residents (3,503 men, 4,880 women; aged ≥30 years) from 300 randomly selected areas participated in the survey, with a participation rate of 76.5% (8,383 of 10,956). We excluded those who met the following criteria: 4,690 participants who were aged <45 years and aged ≥65 years in 1990 (i.e., baseline), 47 participants who had a history of stroke in 1990, 272 participants with missing baseline data and 1,586 participants who were lost to follow up or had no record of living status nor any activities of daily living (ADL) investigation in the 22‐year follow up. Thus, 1,788 were eligible for the analysis. NIPPON DATA90, National Integrated Project for Prospective Observation of Non‐communicable Disease and its Trends in the Aged 1990.
Baseline examination
The baseline survey that was carried out in 1990 included physical examinations, blood tests, and self‐administered questionnaires on medical history and lifestyle. Body mass index (BMI) was calculated as weight in kilograms divided by the square of height in meters. Public health nurses obtained lifestyle data, including smoking and drinking habits, current health status, and medical history. A smoking habit was categorized into non‐smoker, past smoker and current smoker. A drinking habit was categorized into non‐drinker, past drinker and current drinker. Trained observers measured baseline blood pressure using a standard mercury sphygmomanometer on the right arm of seated participants after at least 5 min of rest.
The casual blood samples were obtained at the baseline survey. The serum was separated and centrifuged soon after blood coagulation. The casual blood samples were categorized as fasting plasma glucose (≥4 h) and casual plasma glucose (<4 h) according to the following time intervals after meals: <0.5 h (5.8%); 0.5 to <1 h (5.7%); 1 to <2 h (10.0%); 2 to <3 h (20.9%), 3 to <4 h (18.9%); 4 to <6 h (30.2%); and 6 to <8 h (8.5%). Plasma samples were collected in siliconized tubes containing sodium fluoride and shipped to a laboratory (SRL, Tokyo, Japan) for blood measurements. Plasma glucose was measured enzymatically. Glycated hemoglobin (HbA1c; Japan Diabetes Society [JDS]) was measured by high‐performance liquid chromatography. The coefficient of variation range of HbA1c measurement in this laboratory was 1.19–1.79% intra‐assay and 0.24–0.45% interassay 19 . In the present study, HbA1c (JDS) values were converted to HbA1c (National Glycohemoglobin Standardization Program [NGSP]) values using the conversion formula provided by JDS: HbA1c NGSP value (%) = 1.02 × JDS value (%) + 0.25 16 .
Serum triglycerides and total cholesterol were measured using enzymatic methods, and high‐density lipoprotein cholesterol was measured after heparin–calcium precipitation 20 . Lipid measurements were standardized by the Centers for Disease Control/National Heart, Lung, and Blood Institute Lipids Standardization program. We defined cardiovascular risk factors as follows: hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥ 90 mmHg) or on treatment for hypertension; hypercholesterolemia (total cholesterol ≥240 mg/dL) and/or medication for hypercholesterolemia; low serum high‐density lipoprotein cholesterol (<40 mg/dL); and high serum triglyceride (>150 mg/dL) as serum total cholesterol ≥240 mg/dL.
Exposures: Diabetes categories
Diagnosis of prediabetes and diabetes was ascertained using a comprehensive method of medical treatment for diabetes, fasting plasma glucose (FPG; defined as no caloric intake for at least 4 h) and HbA1c (NGSP value), which was based on the Americans Diabetes Association's diagnostic criteria for diabetes in 2020 21 . The participants were categorized as follows: normoglycemia, both FPG <100 mg/dL (<5.6 mmol/L) and HbA1c <5.7% (39 mmol/mol), and no treatment for diabetes; prediabetes defined by FPG 100–125 mg/dL (5.6–6.9 mmol/L) or HbA1c 5.7%–6.4% (39–46 mmol/mol), or both, and no treatment for diabetes; and diabetes, FPG ≥126 mg/dL (≥7.0 mmol/L) or HbA1c ≥6.5% (47 mmol/mol), or both, or receiving treatment for diabetes regardless of FPG or HbA1c.
Outcomes: Disability and death without disability
As each participant visited a local public health center by themselves at the baseline in the 1990 examination, we assumed that they did not have any difficulties associated with ADL. In the pooled survey, over a 22‐year follow up, participants aged ≥65 years who had reached age 65 years at four time points (1995, 2000, 2006, 2012) were eligible for the ADL survey. The ADL survey was carried out by face‐to‐face interviews at home, telephone interviews, a questionnaire sent by mail or other methods.
The modified questionnaire from Katz et al. 22 included six basic ADL items (eating and drinking, changing clothes, bathing, toileting, and walking indoors and outdoors), and participants were asked to answer either independently, with partial support or with full support for each item. Participants who required partial support or full support to carry out at least one of their six basic ADL items were considered to have a disability. According to their living status for the period of study, the participants who were still alive at the end of the study without observation of ADL decline were considered as “normal”, and participants without observation of ADL decline who died before the next ADL survey were considered as “death without an observation of ADL decline” (death without disability). The participants who died after having observation of ADL decline were also considered as having disability (death with disability).
Vital statistics were obtained from the Management and Coordination Agency, Government of Japan, at the follow‐up survey. Because an existence of a competing risk of disability and death was considered, death without observation of disability was assessed as an outcome separately.
Statistical analysis
Continuous data are presented as the mean ± standard deviation, and frequency data are presented as n (%). The χ2‐test and Student's t‐test were used to test the differences in proportion and means, as appropriate, in the baseline characteristics categorized by baseline glucose tolerance status. Because it was difficult to establish the exact timing when participants experienced disability, and to avoid the competing risk of disability and death occurring, we used the multinomial logit model to estimate odds ratios (OR) and 95% confidence intervals (CI) for incident disability and death without having disability over 22 years of follow up among participants with prediabetes and diabetes compared with normoglycemia participants.
We carried out the analyses without any adjustment (crude) for the first step, then we used a series of multinomial logit models that were adjusted for the following baseline characteristics: demographics, cardiovascular risk factors to examine the association between baseline glucose tolerance status and disability, and death without disability at 22‐year follow up. The multinomial logit models were adjusted as follows: model 1: age, sex, smoking status and alcohol drinking status; model 2: model 1 and cardiovascular risk factors (hypertension, hypercholesterolemia, triglycerides, low serum high‐density lipoprotein); model 3: model 1 and BMI only; and model 4, the final fully adjusted model including all previous variables. ORs and 95% CIs were used, P‐values <0.05 were significant. We also carried out the analysis stratified by sex, because the association might differ by sex.
All statistical analysis was carried out using Stata version 14.2 (StataCorp, College Station, TX, USA). Statistical significance was defined by a two‐sided P‐value <0.05.
RESULTS
Baseline characteristics
In the present study, among 1,788 participants aged 45–64 years at baseline in 1990 who were included in longitudinal analysis, 565 (31.6%) were identified as having prediabetes and 215 (12.0%) as having diabetes at baseline in 1990 (Table 1). Men had a slightly higher proportion of diabetes than women (men 14.2% vs women 10.4%). In contrast, women had a higher proportion of prediabetes than men (women 32.1% vs men 30.9%). The mean ages of participants with prediabetes and diabetes were 58.2 and 58.6, respectively. The mean duration of follow up among participants ranged from 19.0 (±4.5) to 20.5 (±3.5) years. Participants with prediabetes and diabetes had a higher proportion of hypertension and lipidemia than individuals with normal glucose tolerance (63.6% and 68.5%, respectively). There was a significant difference in the distribution of all baseline characteristics, except drinking status, among diabetes categories. Details of other baseline characteristics of respondents are shown in Table 1.
Table 1.
General characteristics of the study population for 1,788 men and women aged 45–64 years according to blood glucose status at baseline in 1990, NIPPON DATA90
| Normal | Prediabetes | Diabetes | P‐values | |
|---|---|---|---|---|
| All participants (%) | 1,008 (56.4) | 565 (31.6) | 215 (12.0) | |
| Men | 420 (54.9) | 237 (30.9) | 109 (14.2) | 0.046 |
| Women | 588 (57.5) | 328 (32.1) | 106(10.4) | |
| Mean age, years (SD) | 56.9 (4.3) | 58.2 (4.2) | 58.6 (4.3) | <0.001 |
| Men | 57.1 (4.3) | 58.1 (4.4) | 58.7 (4.2) | <0.001 |
| Women | 56.8 (4.3) | 58.0 (4.3) | 58.4 (4.2) | <0.001 |
| Mean BMI (SD) | 23.2 (2.9) | 23.5 (3.4) | 23.8 (3.7) | <0.001 |
| Hypertension, n (%) | ||||
| SBP ≥140 mmHg or DBP ≥90 mmHg | 529 (52.5) | 359 (63.6) | 147 (68.7) | <0.001 |
| Hypercholesterolemia, n (%) | ||||
| TCH ≥240 mg/dL | 191 (18.9) | 118 (20.9) | 63 (29.3) | 0.002 |
| Low serum HDL | ||||
| HDL <40 mg/dL | 158 (15.7) | 99 (17.5) | 55 (25.6) | 0.003 |
| Hypertriglyceridemia | ||||
| TG ≥150 mg/dL | 300 (29.8) | 199 (35.2) | 100 (46.5) | <0.001 |
| HbA1c% (mmol/mol) (n and %) | ||||
| <5.7 (<39) | 1,008 (100) | 410 (72.6) | 83 (38.6) | <0.001 |
| 5.7 to <6.5 (39 to <48) | – | 155 (27.4) | 44 (20.5) | |
| ≥6.5 (≥48) | – | – | 88 (40.9) | |
| Smoking status, n (%) | ||||
| Never smoke | 651 (64.6) | 355 (62.8) | 113 (52.6) | 0.016 |
| Ex‐smoker | 111 (11.0) | 62 (11.0) | 36 (16.7) | |
| Current smoker | 246 (24.4) | 148 (26.2) | 66 (30.7) | |
| Alcohol drinking status, n (%) | ||||
| Never drink | 681 (67.5) | 382 (67.6) | 132 (61.4) | 0.183 |
| Ex‐drinker | 22 (2.2) | 14 (2.5) | 10 (4.7) | |
| Current drinker | 305 (30.3) | 169 (29.9) | 73 (33.9) | |
Data are given as the mean (standard deviation) or as n (percentage). DBP, diastolic blood pressure; HDL, high‐density lipoprotein; SBP, systolic blood pressure; TCH, total cholesterol; TG, triglycerides.
Proportions of disability and death without disability according to baseline glucose status
During the 22‐year follow‐up, 334 (18.6%) were reported as having disability and 350 (19.5%) as death without disability. Participants with prediabetes and diabetes reported a higher proportion of disability and death without an observation of disability than individuals with normal glucose tolerance (21.9% and 23.8%, and 23.2% and 27.4%, respectively). In general participants, women reported a higher proportion of disability than men (22% vs 14.2%), whereas men had a higher proportion of death without disability than women (28.5% vs 12.9%). Women with prediabetes reported a higher proportion of disability and death without disability than men with prediabetes (39.6% vs 32.1%, and 38.6% vs 36.7%, respectively). In contrast, men with diabetes reported a higher proportion of disability and death without disability than women with diabetes (16.5% vs 14.7%, and 17.4% vs 15.9%, respectively; Table 2).
Table 2.
Functional ability with living status according to baseline glucose tolerance status at 22‐year follow up for 1,788 men and women aged 45–64 years at baseline
| Normal | Prediabetes | Diabetes | P‐values | |
|---|---|---|---|---|
| Functional ability status | ||||
| Total study population | ||||
| Without disability | 689 (68.3) | 310 (54.9) | 105 (48.8) | <0.001 |
| Disability | 159 (15.8) | 124 (21.9) | 51 (23.8) | |
| Death without disability | 160 (15.9) | 131 (23.2) | 59 (27.4) | |
| Men | ||||
| Without disability | 264 (60.1) | 122 (27.8) | 53 (12.1) | 0.012 |
| Disability | 56 (51.4) | 35 (32.1) | 18 (16.5) | |
| Death without disability | 100 (45.9) | 80 (36.7) | 38 (17.4) | |
| Women | ||||
| Without disability | 425 (63.9) | 188 (28.3) | 52 (7.8) | <0.001 |
| Disability | 103 (45.7) | 89 (39.6) | 33 (14.7) | |
| Death without disability | 60 (45.5) | 51 (38.6) | 21 (15.9) | |
Data are given as n (percentage).
Associations of baseline glucose status and disability
In multinomial logistic regression analysis, the risk of disability was higher in participants with diabetes and prediabetes than participants with normal glucose tolerance, this observation was seen in all models. After we adjusted for all variables in the final model (model 4), the associations of baseline glucose status and disability were still statistically significant, participants with prediabetes and diabetes reported a 43% (OR 1.43, 95% CI 1.07–1.91) and 66% (OR 1.66, 95% CI 1.10–2.50) higher risk of disability than participants with normal glucose tolerance, respectively (Table 3).
Table 3.
Association between baseline glucose tolerance status and activities of daily living status at 22‐year follow up
| Normal | Prediabetes | Diabetes | |||
|---|---|---|---|---|---|
| Adjusted OR (95% CI) | P‐values | Adjusted OR (95% CI) | P‐values | ||
| Disability | |||||
| Model 1 | 1.00 (Reference) | 1.47 (1.10–1.95) | 0.008 | 1.73 (1.16–2.59) | 0.007 |
| Model 2 | 1.00 (Reference) | 1.45 (1.09–1.92) | 0.011 | 1.69 (1.12–2.54) | 0.011 |
| Model 3 | 1.00 (Reference) | 1.44 (1.08–1.93) | 0.011 | 1.68 (1.12–2.52) | 0.011 |
| Model 4 | 1.00 (Reference) | 1.43 (1.07–1.91) | 0.014 | 1.66 (1.10–2.50) | 0.014 |
| Death without disability | |||||
| Model 1 | 1.00 (Reference) | 1.59 (1.19–2.13) | 0.002 | 1.80 (1.20–2.68) | 0.004 |
| Model 2 | 1.00 (Reference) | 1.55 (1.16–2.08) | 0.003 | 1.75 (1.17–2.63) | 0.007 |
| Model 3 | 1.00 (Reference) | 1.59 (1.19–2.12) | 0.002 | 1.80 (1.21–2.69) | 0.004 |
| Model 4 | 1.00 (Reference) | 1.56 (1.16–2.08) | 0.003 | 1.77 (1.18–2.65) | 0.006 |
Data are odds ratios (95% confidence intervals). Model 1: adjusted for age, sex, smoking status and drinking status. Model 2: adjustments in model 1 plus cardiovascular risk factors (hypertension, hypertriglyceridemia and low high‐density lipoprotein, hypercholesterolemia). Model 3: adjustments in model 1 plus body mass index. Model 4 was adjusted for all variables.
Associations of baseline glucose status and death without disability
We evaluated the association between the risk of all‐cause mortality without disability according to baseline glucose status. We found an increased risk of death without disability in participants with diabetes and prediabetes, as they reported a 59% (OR 1.59, 95% CI 1.19–2.13) and 80% (OR 1.80, 95% CI 1.20–2.68) higher risk of death without disability than participants with normal glucose tolerance (model 1), respectively (Table 3). In the final model (model 4), odds ratios slightly decreased in the participants with prediabetes and diabetes (1.56 [OR 1.56, 95% CI 1.16–2.08] and 1.77 [OR 1.77, 95% CI 1.18–2.65], respectively; Table 3).
Associations of disability and death without disability according to baseline glucose status, stratified by sex
Although we did not find an interaction between sex and diabetes status, we carried out a stratified analysis by sex to clarify the effect of baseline glucose status on disability and death without disability within sex groups (Table 4). Among women participants, after full adjustment for all variables in the final model (model 4), women with prediabetes and diabetes had 1.57‐fold (OR 1.57, 95% CI 1.10–2.24) and 2.20‐fold (OR 2.20, 95% CI 1.29–3.76) higher ORs of disability than others, respectively (Table 4). The same observation was reported among those who were reported as death without disability, women with prediabetes and diabetes also reported higher odds ratios of mortality than participants with normal glucose tolerance (OR 1.61, 95% CI 1.05–2.49; OR, 2.35 95% CI 1.26–4.39, respectively) (Table 4). In contrast, the statistically significant association was not found among men with diabetes and prediabetes after adjustment for all variables.
Table 4.
Association between baseline glucose tolerance status and activities of daily living status at 22‐year follow up, stratified by sex
| Men | Women | |||||||
|---|---|---|---|---|---|---|---|---|
| Prediabetes | Diabetes | Prediabetes | Diabetes | |||||
| Adjusted OR (95% CI) | P‐values | Adjusted OR (95% CI) | P‐values | Adjusted OR (95% CI) | P‐values | Adjusted OR (95% CI) | P‐values | |
| Disability | ||||||||
| Model 1 | 1.18 (0.72–1.94) | 0.499 | 1.24 (0.66–2.35) | 0.505 | 1.62 (1.14–2.31) | 0.007 | 2.21 (1.31–3.73) | 0.003 |
| Model 2 | 1.17 (0.71–1.92) | 0.527 | 1.23 (0.64–2.37) | 0.518 | 1.59 (1.12–2.27) | 0.010 | 2.23 (1.30–3.79) | 0.003 |
| Model 3 | 1.18 (0.72–1.94) | 0.500 | 1.22 (0.64–2.33) | 0.540 | 1.58 (1.12–2.26) | 0.010 | 2.15 (1.27–3.64) | 0.004 |
| Model 4 | 1.17 (0.71–1.93) | 0.524 | 1.22 (0.63–2.35) | 0.547 | 1.57 (1.10–2.24) | 0.012 | 2.20 (1.29–3.76) | 0.004 |
| Death without disability | ||||||||
| Model 1 | 1.51 (1.01–2.25) | 0.042 | 1.44 (0.86–2.25) | 0.166 | 1.67 (1.08–2.56) | 0.020 | 2.31 (1.25–4.25) | 0.007 |
| Model 2 | 1.47 (0.99–2.20) | 0.057 | 1.42 (0.83–2.43) | 0.197 | 1.63 (1.05–2.51) | 0.028 | 2.36 (1.26–4.41) | 0.007 |
| Model 3 | 1.53 (1.02–2.27) | 0.038 | 1.48 (0.87–2.52) | 0.141 | 1.65 (1.06–2.54) | 0.024 | 2.27 (1.23–4.19) | 0.009 |
| Model 4 | 1.49 (0.99–2.25) | 0.052 | 1.45 (0.85–2.48) | 0.170 | 1.61 (1.05–2.49) | 0.030 | 2.35 (1.26–4.39) | 0.007 |
Data are odds ratios (95% confidence intervals). Model 1: adjusted for age, smoking status, and drinking status. Model 2: adjustments in model 1 plus cardiovascular risk factors (hypertension, hypertriglyceridemia and low high‐density lipoprotein, hypercholesterolemia). Model 3: adjustments in model 1 plus body mass index. Model 4 was adjusted for all variables.
DISCUSSION
The present longitudinal cohort study was the first study to be carried out in Asia that used longitudinal analysis and repeated measurements in middle‐aged adults, with a focus on the relative association between prediabetes in middle‐aged population with disability and mortality in later life. Our findings support the conceptual framework that middle‐aged adults with prediabetes have higher risks of disability and death without disability than individuals with normal glucose tolerance. Middle‐aged women with blood glucose tolerance disorder were more likely to be associated with disability and mortality at 22‐year follow up than others. Furthermore, the present results support the hypothesis that middle‐aged participants with diabetes have higher ORs of disability and mortality.
In NIPPON DATA90, the study population was randomly selected from 300 community areas in Japan. In the present study, the prevalence of diabetes among middle‐aged Japanese adults was close to another survey on the trends of diabetes in Japan 23 . Furthermore, the proportion of middle‐aged adults with prediabetes was similar to a study carried out among a working‐age population 20 . The present study found that middle‐aged adults with blood glucose tolerance disorder had higher risks of disability and mortality than people without these conditions at later life.
Disability among participants with prediabetes and diabetes were 1.43‐ and 1.66‐fold higher, respectively, than participants with normal glucose tolerance in the present study. Our results are comparable with other studies that were carried out in different populations with various age groups, although the disability definitions were slightly different 6 . In a cross‐sectional study for diabetes carried out in Canadian people aged ≥45 years, which used the OARS (Older Americans Resources and Services) Multidimensional Functional Assessment Questionnaire (OMFAQ) scale to measure functional disability in ADL, Griffith et al. 24 reported that diabetes made the largest contribution to ADL‐related functional disability in middle‐aged adults and older people. In a 1997–1999 National Health Interview Survey study in a USA population, activities limitations (as measured by nine physical tasks) were nearly twofold more common in USA adults with diabetes than in those without diabetes 25 . In addition, a longitudinal study carried out by Koye et al. 7 also found that people with diabetes aged >47 years at baseline were more likely to report more limitations (using Katz ADL questionnaire 6 items) than participants with normal glucose tolerance after 12 years. However, their study found no significant association between a diagnosis of prediabetes at baseline and disability. Another study among middle‐aged adults (aged >53 years) in a USA population found that people with prediabetes were 1.48‐fold more likely to report physical functional limitations (using the Katz ADL scale 5 items) 26 . The present findings that middle‐aged participants with prediabetes had a higher risk of disability than participants with normal glucose tolerance are consistent with these other studies.
Furthermore, the present study supports the hypothesis that people with diabetes have a higher risk of mortality than individuals with normal glucose tolerance. Moreover, we found that a diagnosis of prediabetes in middle‐aged adults significantly increased the risk of mortality in their later life. Meanwhile, other studies reported non‐significant relationships of prediabetes and mortality in elderly populations using cross‐sectional designs 27 , 28 . The differences of population age and study design might lead to different results.
In the present study, we found that women with prediabetes were significantly more likely to be associated with disability and mortality than participants with normal glucose tolerance. A similar finding was found in women with diabetes. However, we did not find significant findings among men. The present findings are consistent with other studies that reported a similar pattern within sex subgroups. Women with diabetes had greater comorbidity, and were more likely to be taking medications that increase the risk of falling and decrease bone mineral density. Compared with men, women have a longer duration of life with disability, in part due to the higher prevalence of non‐fatal chronic conditions; constitutional factors, such as lower muscle strength and lower bone density; and higher rates of lifestyle factors, such as sedentary behavior and obesity 29 , 30 . Japanese women spend their lifetime with more disability than men. The higher prevalence of fragility fractures and dementia, along with higher life expectancy that was reported in other studies among Japanese women, could extend the understanding for this finding 31 , 32 , 33 . The association between men with prediabetes and death without disability is inconsistent after adjusted for all variables, and the association among men with prediabetes with death without disability was significant adjusted for BMI only. A previous study suggested that men with initial BMI <21.7 at age 20 years was associated with twofold increased risk of coronary heart disease, but not in men with initial BMI ≥21.7 34 . In addition to their finding, men with prediabetes reported a higher proportion of BMI <21.7 than men with diabetes in our study.
Disability is considered a long‐term effect for people with diabetes. People with diabetes and prediabetes spend their lifetime with poor quality of life 35 , 36 , 37 . The relationship between diabetes and disability is multifactorial, has modifiable factors, and varies between men and women. An appropriate prevention program that focuses on middle‐aged adults with prediabetes might slow the progression to diabetes, reduce the incidence of functional limitations and mortality in later life, improve quality of life, reduce the cost of healthcare visits, and lessen the burden on their spouse and society.
The present study had several strengths. First, the sampling collection was randomly carried out around Japan; thus, the results are generally representative among Japanese people, and can be applied for middle‐aged adults in other similar communities. Second, we used a comprehensive method with three diagnostic criteria to categorize the baseline blood glucose tolerance status, which lessened the underreporting diabetes rate and reduced recall bias; thus, overcoming the main limitations reported in previous studies. Third, our longitudinal design with repeated measures provides more precise estimates for the outcome of interest than the previous cross‐sectional studies. Our study was limited by the lack of a baseline ADL survey in 1990. We also underestimated the development of baseline blood glucose tolerance status over the 22‐year follow up. In addition, we were unable to establish the exact time of disability due to the discrete time point of the survey; thus, the development of disability along with blood glucose status could not be clarified. Due to the sample sizes, we could not analyze by 5‐year interval age groups, although the age groups had different number of chances for the ADL survey due to the study design. We could not assess the type of diabetes mellitus due to lack of detailed information.
In summary, prediabetes in middle‐aged adults is a predictor for disability and increases the risk of mortality in later life, especially in women. Early screening and intervention might decrease the progression of diabetes and its complications. Other prominent factors need to be considered to explore the causal relationship between prediabetes and disability in further studies.
DISCLOSURE
The authors declare no conflict of interest.
Approval of the research protocol: R2005‐021 (The ethics committee of Shiga University of Medical Science).
Informed consent: N/A.
Registry and the registration no. of the study/trial: N/A.
Animal studies: N/A.
Supporting information
Appendix S1 | Aknowledgements and the member list of NIPPON DATA80/90 Research Group.
ACKNOWLEDGMENTS
This study was supported by a Grant‐in‐Aid from the Ministry of Health, Labor and Welfare under the auspices of the Japanese Association for Cerebro‐cardiovascular Disease Control; a Research Grant for Cardiovascular Diseases (7A‐2) from the Ministry of Health, Labor and Welfare; and Health and Labor Sciences Research Grants, Japan (Comprehensive Research on Aging and Health [H11‐Chouju‐046, H14‐Chouju‐003, H17‐Chouju‐012, H19‐Chouju‐Ippan‐014] and Comprehensive Research on Life‐Style Related Diseases including Cardiovascular Diseases and Diabetes Mellitus [H22‐Junkankitou‐Seishuu‐Sitei‐017, H25‐Junkankitou‐Seishuu‐Sitei‐022, H30‐Junkankitou‐Sitei‐002, 21FA2002]). The authors thank all members of the Japanese Association of Public Health Center Directors and all staff of the public health centers that cooperated with our study.
REFERENCES
- 1. Lin X, Xu Y, Pan X, et al. Global, regional, and national burden and trend of diabetes in 195 countries and territories: an analysis from 1990 to 2025. Sci Rep 2020; 10: 14790. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Ministry of Health Law . Vital Statistics of Japan 2018. Tokyo: Ministry of Health, Labour and Welfare, 2018. [Google Scholar]
- 3. Masakane I, Nakai S, Ogata S, et al. An overview of regular dialysis treatment in Japan (As of 31 December 2013). Ther Apher Dial 2015; 19: 540–574. [DOI] [PubMed] [Google Scholar]
- 4. Harding JL, Pavkov ME, Magliano DJ, et al. Global trends in diabetes complications: a review of current evidence. Diabetologia 2019; 62: 3–16. [DOI] [PubMed] [Google Scholar]
- 5. Huo L, Shaw JE, Wong E, et al. Burden of diabetes in Australia: life expectancy and disability‐free life expectancy in adults with diabetes. Diabetologia 2016; 59: 1437–1445. [DOI] [PubMed] [Google Scholar]
- 6. McGrath RP, Vincent BM, Snih SA, et al. The association between handgrip strength and diabetes on activities of daily living disability in older Mexican Americans. J Aging Health 2018; 30: 1305–1318. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. Koye DN, Shaw JE, Magliano DJ. Diabetes and disability in older Australians: the Australian Diabetes, Obesity and Lifestyle (AusDiab) study. Diabetes Res Clin Pract 2017; 126: 60–67. [DOI] [PubMed] [Google Scholar]
- 8. Wong E, Woodward M, Stevenson C, et al. Prevalence of disability in Australian elderly: impact of trends in obesity and diabetes. Prev Med 2016; 82: 105–110. [DOI] [PubMed] [Google Scholar]
- 9. Wong E, Backholer K, Gearon E, et al. Diabetes and risk of physical disability in adults: a systematic review and meta‐analysis. Lancet Diabetes Endocrinol 2013; 1: 106–114. [DOI] [PubMed] [Google Scholar]
- 10. McGrath R, Al Snih S, Markides K, et al. The burden of functional disabilities for middle‐aged and older adults in the United States. J Nutr Health Aging 2019; 23: 172–174. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Shang Y, Fratiglioni L, Vetrano DL, et al. Not only diabetes but also prediabetes leads to functional decline and disability in older adults. Diabetes Care 2021; 44: 690–698. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Gregg EW, Cheng YJ, Srinivasan M, et al. Trends in cause‐specific mortality among adults with and without diagnosed diabetes in the USA: an epidemiological analysis of linked national survey and vital statistics data. Lancet 2018; 391: 2430–2440. [DOI] [PubMed] [Google Scholar]
- 13. Salinas JJ, Gonzalez JMR, Al SS. Type 2 diabetes, depressive symptoms and disability over a 15‐year follow‐up period in older Mexican Americans living in the southwestern United States. J Diabetes Complications 2018; 32: 75–82. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. Fong JH. Disability incidence and functional decline among older adults with major chronic diseases. BMC Geriatr 2019; 19: 323. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Kadota A, Hozawa A, Okamura T, et al. Relationship between metabolic risk factor clustering and cardiovascular mortality stratified by high blood glucose and obesity: NIPPON DATA90, 1990‐2000. Diabetes Care 2007; 30: 1533–1538. [DOI] [PubMed] [Google Scholar]
- 16. Okamura T, Hayakawa T, Kadowaki T, et al. The inverse relationship between serum high‐density lipoprotein cholesterol level and all‐cause mortality in a 9.6‐year follow‐up study in the Japanese general population. Atherosclerosis 2006; 184: 143–150. [DOI] [PubMed] [Google Scholar]
- 17. Nakamura K, Okamura T, Hayakawa T, et al. Electrocardiogram screening for left high R‐wave predicts cardiovascular death in a Japanese community‐based population: NIPPON DATA90. Hypertens Res 2006; 29: 353–360. [DOI] [PubMed] [Google Scholar]
- 18. Higashiyama A, Hozawa A, Murakami Y, et al. Prognostic value of q wave for cardiovascular death in a 19‐year prospective study of the Japanese general population. J Atheroscler Thromb 2009; 16: 40–50. [DOI] [PubMed] [Google Scholar]
- 19. Kashiwagi A, Kasuga M, Araki E, et al. International clinical harmonization of glycated hemoglobin in Japan: From Japan Diabetes Society to National Glycohemoglobin Standardization Program values. Diabetology International 2012; 3: 8–10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. Uehara A, Kurotani K, Kochi T, et al. Prevalence of diabetes and pre‐diabetes among workers: Japan Epidemiology Collaboration on Occupational Health Study. Diabetes Res Clin Pract 2014; 106: 118–127. [DOI] [PubMed] [Google Scholar]
- 21. Association AD. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2020. Diabetes Care 2020; 43(Suppl. 1): S14–S31. [DOI] [PubMed] [Google Scholar]
- 22. Katz S, Downs TD, Cash HR, et al. Progress in development of the index of ADL. Gerontologist 1970; 10: 20–30. [DOI] [PubMed] [Google Scholar]
- 23. Ikeda N, Nishi N, Noda H, et al. Trends in prevalence and management of diabetes and related vascular risks in Japanese adults: Japan National Health and Nutrition Surveys 2003‐2012. Diabetes Res Clin Pract 2017; 127: 115–122. [DOI] [PubMed] [Google Scholar]
- 24. Griffith L, Raina P, Wu H, et al. Population attributable risk for functional disability associated with chronic conditions in Canadian older adults. Age Ageing 2010; 39: 738–745. [DOI] [PubMed] [Google Scholar]
- 25. United States Department Of Health And Human Services. Centers For Disease Control And Prevention, National Center For Health Statistics, National Health Interview Survey . 1999. ICPSR ‐ Interuniversity Consortium for Political and Social Research. 10.3886/ICPSR03397.V1 [DOI]
- 26. Lee, PG , Cigolle, CT , Ha, J , et al. Physical function limitations among middle-aged and older adults with prediabetes: one exercise prescription may not fit all. Diabetes Care 2013; 36: 3076–3083. 10.2337/dc13-0412 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27. Deedwania P, Patel K, Fonarow GC, et al. Prediabetes is not an independent risk factor for incident heart failure, other cardiovascular events or mortality in older adults: findings from a population‐based cohort study. Int J Cardiol 2013; 168: 3616–3622. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. Tang O, Matsushita K, Coresh J, et al. Mortality implications of prediabetes and diabetes in older adults. Diabetes Care 2019; 43: 382–388. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29. Chau DL, Edelman SV, Chandran M. Osteoporosis and diabetes. Curr Diab Rep 2003; 3: 37–42. [DOI] [PubMed] [Google Scholar]
- 30. Lipscombe LL, Jamal SA, Booth GL, et al. The risk of hip fractures in older individuals with diabetes. Diabetes Care 2007; 30: 835–841. [DOI] [PubMed] [Google Scholar]
- 31. Thein FS, Li Y, Nyunt MSZ, et al. Physical frailty and cognitive impairment is associated with diabetes and adversely impact functional status and mortality. Postgrad Med 2018; 130: 561–567. [DOI] [PubMed] [Google Scholar]
- 32. Montgomery W, Ueda K, Jorgensen M, et al. Epidemiology, associated burden, and current clinical practice for the diagnosis and management of Alzheimer's disease in Japan. Clinicoecon Outcomes Res 2018; 10: 13–28. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33. Tsuda T. Epidemiology of fragility fractures and fall prevention in the elderly: a systematic review of the literature. Curr Orthop Pract 2017; 28: 580–585. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34. Chei CL, Iso H, Yamagishi K, et al. Body mass index and weight change since 20 years of age and risk of coronary heart disease among Japanese: the Japan Public Health Center‐Based Study. Int J Obes (Lond) 2008; 32: 144–151. [DOI] [PubMed] [Google Scholar]
- 35. Choi YS, Kim MJ, Lee GY, et al. The association between frailty and disability among the elderly in rural areas of Korea. Int J Environ Res Public Health 2019; 16: 2481. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36. Quinones A, Markwardt S, Botoseneanu A. Associations of multimorbidity combinations including diabetes with disability among middle‐aged and older adults. Innov Aging 2018; 2(suppl. 1): 477. [Google Scholar]
- 37. Tyrer F, Ling S, Bhaumik S, et al. Diabetes in adults with intellectual disability: prevalence and associated demographic, lifestyle, independence and health factors. J Intellect Disabil Res 2020; 64: 287–295. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Appendix S1 | Aknowledgements and the member list of NIPPON DATA80/90 Research Group.