Introduction
Falls are a major public health problem that causes considerable morbidity and affects the quality of life of people around the world [
1]. Several risk factors for falls, such as age, physical inactivity, loss of balance, and loss of vision, have been identified. Due to both complications of their disease and a direct effect of the disease on bone quality, patients with type 2 diabetes are thought to have an increased fall and fracture risk [
2,
3]. However, conflicting results about fall and fracture risk in patients with type 2 diabetes have been described. Compared to subjects with normal glucose metabolism, fall and fracture risk may be either comparable or increased in patients with type 2 diabetes [
3‐
10]. These different results may be explained by differences in the way diabetes has been diagnosed (self-reported vs. an oral glucose tolerance test (OGTT)) and how falls and fractures have been reported (retrospective vs. prospective). Furthermore, indicators of diabetes severity such as the degree of glucose control, the duration of disease, and the prevalence of insulin use are often not reported. This may have resulted in study populations with different levels of exposure and, consequently, different results [
4,
5,
7,
8,
10].
Only few studies about fracture risk and no studies about fall risk in people with impaired glucose metabolism (defined as either impaired fasting glucose or impaired glucose tolerance) have been published. People with impaired glucose metabolism are often overweight, which is associated with a decreased fracture risk [
11], and have increased serum levels of insulin [
12], which stimulates bone formation. It may therefore be hypothesized that people with impaired glucose metabolism have a decreased fracture risk. Previous studies indeed showed a normal to decreased fracture risk in people with impaired glucose metabolism when compared to people with normal glucose metabolism [
6,
12,
13].
In the present study, we examined the association between glucose metabolism status and recent falls and previous fractures in a well-characterized cohort of participants from the Maastricht Study aged 50 years and older. Additionally, we examined the association between glucose control, insulin use, diabetes duration, and falls in the past 6 months and fractures at or above the age of 50. We hypothesized that the prevalence of falls and fractures in participants with impaired glucose metabolism is similar or decreased when compared to participants with normal glucose metabolism and that the prevalence of falls and fractures in participants with type 2 diabetes is increased only in those with inadequately regulated diabetes, insulin users and those with a long duration of the disease.
Results
General characteristics of the fall analysis population according to glucose metabolism status are shown in Table
1. In total, 1246 participants were classified as having normal glucose metabolism, 359 as having impaired glucose metabolism, and 400 as having type 2 diabetes. Participants with type 2 diabetes were the oldest, the least likely to be female, had the lowest level of education, the highest BMI, and the highest prevalence of depression. Participants with normal glucose metabolism had the lowest prevalence of CVD and the highest prevalence of non-smokers. Alcohol consumption was the lowest in the group with type 2 diabetes. The mean HbA1c level of the group with type 2 diabetes was 7.0 % (53.4 mmol/mol); almost 93 % used antidiabetic drugs, including insulin in 26 %. The median diabetes duration was 7.0 years. The prevalence of a fall in the past 6 months and the number of falls in the past 6 months was not significantly different between the groups, while the prevalence of a fracture at or above the age of 50 was lowest in the group with type 2 diabetes. The general characteristics of the fracture analysis population according to glucose metabolism status were comparable to those of the fall analysis population (not tabulated).
Table 1
General characteristics of the study population by glucose metabolism status
Age (years) | 60.5 (6.1) | 63.0 (5.9) | 63.4 (6.3) | <0.001 |
Female sex | 708 (56.8) | 158 (44.0) | 128 (32.0) | <0.001 |
Level of education |
- Low | 344 (27.6) | 131 (36.5) | 165 (41.3) | <0.001 |
- Medium | 324 (26.0) | 92 (25.6) | 124 (31.0) | |
- High | 578 (46.4) | 136 (37.9) | 111 (27.8) | |
BMI (kg/m2) | 25.5 (3.6) | 27.9 (4.2) | 29.7 (4.7) | <0.001 |
Self-reported MVPA (hours/week) | 6.2 (4.5) | 5.2 (4.2) | 4.4 (4.1) | <0.001 |
History of CVD | 154 (12.4) | 50 (13.9) | 120 (30.0) | <0.001 |
Smoking status |
- Never | 471 (37.8) | 103 (28.7) | 109 (27.3) | <0.001 |
- Former | 645 (51.8) | 219 (61.0) | 241 (60.3) | |
- Current | 130 (10.4) | 37 (10.3) | 50 (12.5) | |
Alcohol consumption category |
- None | 142 (11.4) | 52 (14.5) | 114 (28.5) | <0.001 |
- Low | 715 (57.4) | 194 (54.0) | 217 (54.3) | |
- High | 389 (31.2) | 113 (31.5) | 69 (17.3) | |
Medication use |
- Antidiabetic drugs | – | – | 371 (92.8) | – |
- Insulin | – | – | 104 (26.0) | – |
- Blood pressure lowering drugs | 303 (24.3) | 168 (46.8) | 296 (74.0) | <0.001 |
- Lipid-modifying drugs | 237 (19.0) | 135 (37.6) | 315 (78.8) | <0.001 |
- Sleep medication | 27 (2.2) | 11 (3.1) | 9 (2.3) | 0.61 |
Depression | 21 (1.7) | 9 (2.5) | 20 (5.0) | 0.001 |
MMSE score | 29.2 (1.1) | 28.9 (1.2) | 28.7 (1.4) | <0.001 |
HbA1c (%) | 5.5 (0.3) | 5.7 (0.4) | 7.0 (1.1) | <0.001 |
HbA1c (mmol/mol) | 36.4 (3.7) | 39.0 (4.4) | 53.4 (11.5) | <0.001 |
Duration of diabetes in years, mean (IQR) | – | – | 7.0 (9.0) | – |
Fall in the past 6 months | 204 (16.4) | 72 (20.1) | 66 (16.5) | 0.25 |
Number of falls in the past 6 months |
- 0 | 1042 (83.6) | 287 (79.9) | 334 (83.5) | 0.44 |
- 1 | 134 (10.8) | 51 (14.2) | 42 (10.5) | |
- ≥2 | 70 (5.6) | 21 (5.8) | 24 (6.0) | |
Fracture ≥50 years of age | 119 (10.3) | 40 (12.3) | 19 (5.4) | 0.006 |
Table
2 shows the association between glucose metabolism status and falls or fractures. The odds ratio (OR) for a fall was significantly increased in participants with impaired glucose metabolism (OR (95 % CI) 1.37 (1.01–1.87)) after adjustment for age, sex, and level of education (model 2). After further adjustment (model 3) the OR was no longer statistically significant (OR (95 % CI) 1.28 (0.93–1.77)). The addition of BMI to model 2 resulted in loss of statistical significance (data not shown). When the impaired glucose metabolism group was divided into participants with impaired fasting glucose and in participants with impaired glucose tolerance, the odds for a fall was increased only in participants with impaired glucose tolerance after adjustment for age, sex, and level of education (model 2, OR (95 % CI) 1.42 (1.01–1.99)). The odds for a fall in the group with type 2 diabetes was not statistically significantly different from those with a normal glucose metabolism in all models.
Table 2
The association between glucose metabolism status and falls in the past 6 months or fractures at or above the age of 50
Falls
|
NGM | 204 | 1246 | Ref | Ref | Ref |
IGM | 72 | 359 | 1.28 (0.95–1.73) |
1.37 (1.01–1.87)
| 1.28 (0.93–1.77) |
- IFG | 16 | 93 | 1.06 (0.61–1.86) | 1.25 (0.71–2.20) | 1.16 (0.65–2.07) |
- IGT | 56 | 266 | 1.36 (0.98–1.90) |
1.42 (1.01–1.99)
| 1.32 (0.93–1.89) |
T2DM | 66 | 400 | 1.01 (0.75–1.37) | 1.17 (0.85–1.62) | 0.95 (0.64–1.40) |
Fractures
|
NGM | 119 | 1162 | Ref | Ref | Ref |
IGM | 40 | 326 | 1.23 (0.84–1.80) | 1.20 (0.80–1.78) | 1.28 (0.84–1.95) |
- IFG | 9 | 85 | 1.04 (0.51–2.13) | 1.24 (0.59–2.58) | 1.30 (0.62–2.76) |
- IGT | 31 | 241 | 1.29 (0.85–1.97) | 1.19 (0.76–1.85) | 1.28 (0.81–2.02) |
T2DM | 19 | 359 |
0.49 (0.30–0.81)
|
0.55 (0.32–0.92)
| 0.70 (0.38–1.27) |
The odds for a fracture in the group with impaired glucose metabolism were not statistically significantly different from those with a normal glucose metabolism in all models. The odds for a fracture were significantly decreased in participants with type 2 diabetes after adjustment for age, sex, and level of education (model 2, OR (95 % CI) 0.55 (0.32–0.92)), when compared to participants with normal glucose metabolism. The association was not significantly different anymore after further adjustment for BMI, MVPA, a history of CVD, smoking status, alcohol consumption, the use of blood pressure lowering drugs, lipid-modifying drugs, and sleep medication, and depression and cognitive function (model 3, OR (95 % CI) 0.70 (0.38–1.27)).
Table
3 shows the association between diabetes regulation, insulin use, or diabetes duration and falls or fractures in the group with type 2 diabetes. The mean HbA1c level of the subgroup with an HbA1c >7 % (>53 mmol/mol) was 8.0 ± 1.0 % (64.4 ± 11.4 mmol/mol); the mean HbA1c level of the subgroup with an HbA1c ≤7 % (≤53 mmol/mol) was 6.4 ± 0.4 % (46.9 ± 4.3 mmol/mol). The median duration of diabetes of the subgroup with a diabetes duration >5 years was 11.0 (interquartile range (IQR) 8.0) years, and of the subgroup with a diabetes duration ≤5 years was 3.0 (IQR 2.0) years. The OR for a fall of participants with an HbA1c >7 % (53 mmol/mol), insulin users, or participants with a diabetes duration of more than 5 years was not statistically significantly different from those of participants with an HbA1c ≤7 % (53 mmol/mol), non-insulin users, and those with a duration of 5 years or less, respectively, in all the models. Similarly, there were no statistically significant associations between HbA1c, insulin use, or diabetes duration and fractures.
Table 3
The association between diabetes regulation, insulin use, or duration of diabetes and falls or fractures
Falls
|
HbA1c ≤7 % (53 mmol/mol) | 41 | 250 | Ref | Ref | Ref |
HbA1c >7 % (53 mmol/mol) | 25 | 150 | 1.02 (0.59–1.76) | 1.09 (0.62–1.92) | 1.05 (0.58–1.90) |
Insulin − | 44 | 296 | Ref | Ref | Ref |
Insulin + | 22 | 104 | 1.54 (0.87–2.72) | 1.63 (0.90–2.94) | 1.51 (0.79–2.89) |
Diabetes duration ≤5 years | 30 | 173 | Ref | Ref | Ref |
Diabetes duration >5 years | 36 | 227 | 0.90 (0.53–1.53) | 0.86 (0.50–1.49) | 0.83 (0.46–1.47) |
Fractures
|
HbA1c ≤7 % (53 mmol/mol) | 13 | 225 | Ref | Ref | Ref |
HbA1c >7 % (53 mmol/mol) | 6 | 134 | 0.76 (0.28–2.06) | 0.69 (0.25–1.90) | 0.53 (0.18–1.59) |
Insulin − | 13 | 269 | Ref | Ref | Ref |
Insulin + | 6 | 90 | 1.41 (0.52–3.82) | 1.27 (0.46–3.50) | 1.39 (0.44–4.33) |
Duration of diabetes ≤5 years | 11 | 158 | Ref | Ref | Ref |
Duration of diabetes >5 years | 8 | 201 | 0.55 (0.22–1.41) | 0.50 (0.19–1.31) | 0.52 (0.19–1.44) |
In additional analyses, we examined the association between glucose metabolism status and recurrent falls (data not tabulated). Impaired glucose metabolism and type 2 diabetes were not statistically significantly associated with recurrent falls. Finally, the results of the regression analyses for a fall in the past 6 months or recurrent falls in the past 6 months were similar to those described above, when the fracture analysis population instead of the fall analysis population was used.
Discussion
In this study, we examined the association between glucose metabolism status and a history of fractures and recent falls in a group of 2005 participants at or above the age of 50 from the Maastricht Study. In contrast to our hypothesis, we did not find a significant association between glucose metabolism status and a history of falls or fractures. Diabetes severity, in terms of inadequately regulated disease, insulin use, or duration of diabetes, was also not significantly associated with increased odds of prior fractures or recent falls.
Previous cross-sectional fall studies showed no significant difference in fall rate between participants with and without type 2 diabetes [
9,
19]. However, both studies used a small sample size and only showed results of univariate analyses. The results of previous prospective studies on fall risk in patients with type 2 diabetes are conflicting; some studies showed an increased fall risk [
8,
10,
20,
21], while others showed a fall risk similar to participants without diabetes [
7,
13].
Our study is in line with two out of three previous cross-sectional studies that investigated the association between type 2 diabetes and fractures, where significant association between type 2 diabetes and all types of fractures and hip fractures specifically was showed [
4,
6]. Additionally, no association between an impaired fasting glucose and fractures was shown [
6]. In contrast, two meta-analyses and a recent large prospective study showed an increased fracture risk in patients with type 2 diabetes [
3,
22,
23]. However, none of the prospective fall and fracture studies provided information on HbA1c levels, the percentage of insulin users, and the duration of diabetes. This lack of information hampers the comparison of these studies, since they may have been conducted in patient populations with different characteristics regarding type 2 diabetes.
In our study, participants with type 2 diabetes had generally well-regulated diabetes (mean HbA1c level 7.0 % (53.4 mmol/mol)), a relatively short median duration of the disease (7.0 years), and the percentage of insulin users was low (26.0 %). A potential explanation for the non-significant differences in fall and fracture rate between those with and without type 2 diabetes is that an increased fall and fracture risk is only present in patients with more severe and longer duration of the disease. Indeed, several prospective cohort studies showed that only inadequately regulated diabetes was associated with an increased fall and fracture risk [
13,
24,
25]. In the current, study we did not find statistically significant differences in the odds of falls and fractures in inadequately versus adequately regulated participants with type 2 diabetes, in those with a duration of diabetes >5 years versus ≤5 years, nor between insulin users versus non-insulin users. The cut-off values for HbA1c level and duration of diabetes we chose can be discussed. We used an HbA1c level of 7 % (53 mmol/mol) as cut-off value because this is the target value for diabetes treatment [
26]. The mean HbA1c level of our inadequately regulated group was 8.0 % (64.4 mmol/mol), which is close to the target value and may explain the absence of the different fall and fracture rates between the group with adequately and inadequately regulated diabetes. Only few patients in our cohort of patients with type 2 diabetes had HbA1c levels above 9 %; it was therefore not possible to examine the association between different degrees of glucose metabolism regulation and falls or fractures.
The absolute number of fractures in both of our groups of participants with an impaired glucose metabolism and of participants with type 2 diabetes was very low (n = 40 and n = 19, respectively), which is remarkable given the large number of participants in each group and the fact that quite a high number of participants reported at least one fall in the previous 6 months (N = 66 and N = 56, respectively). Due to this low absolute number of total fractures, there may be a power problem for showing an association between glucose metabolism status and fractures.
The meta-analysis by Janghorbani et al. showed an increased hip fracture risk, but no association between type 2 diabetes and fractures of the distal forearm, proximal humerus, or vertebra [
22]. In contrast, the meta-analysis by Vestergaard et al. showed an increase in wrist fracture risk, but not in non-vertebral and spine fracture risk [
3]. Because of the low absolute number of fractures observed in our study, we were not able to examine specific types of fractures.
To the best of our knowledge, up to this date, no studies have been performed on the association between impaired glucose metabolism and falls. Fracture risk has previously been shown to be normal or decreased in participants with impaired glucose metabolism [
6,
12,
13]. Because most fractures occur due to a fall [
27], a normal to decreased fall risk may be expected. On the other hand, our participants with impaired glucose metabolism were less physically active than participants with normal glucose metabolism and this may lead to some degree of muscle weakness in participants with impaired glucose metabolism and therefore an increased fall risk. Furthermore, the BMI of our participants with impaired glucose metabolism was significantly higher than the BMI of participants with normal glucose metabolism, which could also contribute to an increased falling frequency [
28]. In our study, we found a significant association between impaired glucose metabolism and a fall in the past 6 months after adjustment for demographic factors. The association became non-significant after adjustment for BMI and other confounders, so the increased odds of fall in participants with an impaired glucose metabolism in model 2 may be partly explained by their increased BMI. No statistically significant association between participants with impaired glucose metabolism and fractures was found.
Strengths of this study include the objective determination of the glucose metabolism status in a large study population, the well-characterized study cohort, and the availability of extensive information about our participants with type 2 diabetes. In contrast to many previous studies, glucose metabolism status was determined with an OGTT, which allowed us to compare distinct groups of participants. Information about insulin use, an objectively determined HbA1c level, and the duration of diabetes was well registered for all participants with type 2 diabetes which enabled us to compare different subgroups of participants with type 2 diabetes.
Limitations of our study include the absence of a definition of ‘fall’ in our questionnaire, the cross-sectional study design, the use of retrospectively collected and self-reported data on falls and fractures, and the lack of information about complications of diabetes. According to the PROFANE guideline [
29], a fall should be defined as “an unexpected event in which the participants come to rest on the ground, floor, or lower level.” Due to the absence of this definition, participants may have either reported a fall that did not meet the definition or not reported a fall that did meet the definition. Prospective collection of data on falls using a fall diary and on fractures using radiology rapports is preferable over the use of self-reported falls and fractures. However, previous research showed that the accuracy of both self-reported falls and fractures is reasonable [
30‐
32]. Because data about falls and fractures were collected retrospectively, it is not possible to assess whether participants labeled as having impaired glucose metabolism already had impaired glucose metabolism at the moment of their fall or fracture. Because we wanted to be sure to examine the association between type 2 diabetes and falls and fractures only in participants who already had diabetes at the date of their fall or fracture, we excluded participants with an unknown duration of diabetes and those with an unknown date of the fracture. This may have contributed to the low absolute number of fractures that were left for our analyses. In our study, we used HbA1c level, insulin use, and diabetes duration instead of complications of diabetes as markers of diabetes severity. Future studies are needed to study the association between complications of diabetes and falls and fractures.
In conclusion, glucose metabolism status was not significantly associated with a history of fractures or recent falls. Furthermore, diabetes severity was also not significantly associated with prior fractures or recent falls. This study suggests that the fall and fracture rate may not be increased in relatively young patients with generally well-regulated type 2 diabetes. Prospective cohort studies with an extensively described type 2 diabetes cohort should be performed to confirm these results.
Acknowledgments
This study was supported by the European Regional Development Fund via OP-Zuid, the Province of Limburg, the Dutch Ministry of Economic Affairs (grant 31O.041), Stichting De Weijerhorst (Maastricht, the Netherlands), the Pearl String Initiative Diabetes (Amsterdam, the Netherlands), the Cardiovascular Center (CVC, Maastricht, the Netherlands), Cardiovascular Research Institute Maastricht (CARIM, Maastricht, the Netherlands), School for Public Health and Primary Care (CAPHRI, Maastricht, the Netherlands), School for Nutrition, Toxicology and Metabolism (NUTRIM, Maastricht, the Netherlands), Stichting Annadal (Maastricht, the Netherlands), Health Foundation Limburg (Maastricht, the Netherlands), and by unrestricted grants from Janssen-Cilag B.V. (Tilburg, the Netherlands), Novo Nordisk Farma B.V. (Alphen aan den Rijn, the Netherlands), and Sanofi-Aventis Netherlands B.V. (Gouda, the Netherlands).