Journal of Diabetes and Its Complications xxx (2015) xxx–xxx

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Risk factors associated with falls in elderly patients with type 2 diabetes Yuko Chiba ⁎, Yoshiyuki Kimbara, Remi Kodera, Yuki Tsuboi, Ken Sato, Yoshiaki Tamura, Seijiro Mori, Hideki Ito, Atsushi Araki Department of Diabetes, Metabolism, and Endocrinology, Tokyo Metropolitan Geriatric Hospital, 35–2, Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan

a r t i c l e

i n f o

Article history: Received 12 January 2015 Received in revised form 13 May 2015 Accepted 26 May 2015 Available online xxxx Keywords: Hypoglycemia Falls Elderly type 2 diabetes Impaired balance Sarcopenia Frailty

a b s t r a c t Aims: This study investigated risk factors of falls in elderly patients with type 2 diabetes mellitus. Methods: A total of 211 patients aged ≧60 years (168 diabetic patients and 43 non-diabetic control subjects) were studied. Factors associated with falls in the past year were retrospectively examined using multiple logistic regression analysis. Results: The prevalence of patients who had a history of falls in the past year was twice as high as in diabetic patients compared in control subjects (36.9% vs. 18.6%, P b 0.05). When diabetic patients were exclusively analyzed, the presence of any level of hypoglycemia and the Timed Up and Go test (TUG) scores correlated with patients' falls. The presence of hypoglycemia (OR 3.62, 95% CI: 1.242–10.534, P = 0.018), cognitive impairment (OR 3.63, 95% CI: 1.227–10.727, P = 0.020), and high Fall Risk Index scores (OR 1.2, 95% CI: 1.010–1.425, P = 0.039) was independently correlated with the presence of multiple falls. When the diabetic patients were divided into three groups according to the frequency of hypoglycemia episodes, the prevalence of falls increased as the frequency of hypoglycemia increased. Conclusion: Hypoglycemia was a risk factor of falls in elderly type 2 diabetic patients. © 2015 Elsevier Inc. All rights reserved.

1. Introduction The prevalence of type 2 diabetes mellitus is increasing worldwide, and the disease has become a significant public health problem in individuals of all ages (Zimmet, Alberti, & Shaw, 2001). Falls in diabetic patients may lead to disabilities and a lower quality of life (QOL). Repeated incidence of falls, even if not complicated with fractures, lowers the patient's motivation and ability to perform activities of daily living (Kim et al., 2001). Elderly individuals with type 2 diabetes often exhibit greater impairments in posture and gait and are typically at an increased risk of falling (Maurer, Burcham, & Cheng, 2005; Schwartz et al., 2002). A previous history of falls, poor lower extremity function, poor balance, a history of coronary heart disease (CHD), arthritis, being overweight, musculoskeletal pain, depression, poor vision, polypharmacy including hypnotics, peripheral neuropathy, and insulin therapy is associated with an increased risk of falling in diabetic patients (Volpato, Leveille, Blaum, Fried, & Guralnik, 2005). The relationship between HbA1c and the risk of falls is more likely U-shape at different levels of HbA1c. For example, Yau et al. (2013) reported that hyperglycemia (HbA1c N 8%) as well as poor balance were risk factors for fall injuries requiring hospitalization in elderly diabetic patients. On the contrary, Nelson, Dufraux, and Cook (2007) Conflicts of interest: None. ⁎ Corresponding author. Tel.: +81 3 3964 1141; fax: +81 3 3964 1982. E-mail address: [email protected] (Y. Chiba).

demonstrated that the risk of falls in community-dwelling diabetic patients aged ≧ 75 years markedly increased when HbA1c was ≦ 7%, regardless of their frailty status. A cohort study using well-functioning older adults showed that the use of insulin and a lower glycemic control (HbA1c ≦ 6%) increased the risk of falls, although no correlation between HbA1c level and oral hypoglycemic medications was observed (Schwartz et al., 2008). Johnston, Conner, Aagren, Ruiz, and Bouchard (2012) indicated that severe hypoglycemic events were independently correlated with an increased risk of fall-related fractures, but the relationship between mild hypoglycemia and falls in elderly diabetic patients remains unknown. The aim of the present study was to investigate risk factors of fall in elderly diabetic patients. 2. Materials and methods 2.1. Study participants A total of 211 individuals aged ≧ 60 years, who visited the outpatient clinic of the Department of Diabetes, Metabolism, and Endocrinology, Tokyo Metropolitan Geriatric Hospital, Japan, for at least a year, were recruited for the study. Patients were registered from December 2009 to April 2011. Exclusion criteria included blindness, wheelchair/bedridden condition, end-stage renal disease (dialysis therapy period), advanced-stage dementia (almost cannot communicate), adrenal insufficiency, hypopituitarism, hypo/

http://dx.doi.org/10.1016/j.jdiacomp.2015.05.016 1056-8727/© 2015 Elsevier Inc. All rights reserved.

Please cite this article as: Chiba, Y., et al., Risk factors associated with falls in elderly patients with type 2 diabetes, Journal of Diabetes and Its Complications (2015), http://dx.doi.org/10.1016/j.jdiacomp.2015.05.016

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Y. Chiba et al. / Journal of Diabetes and Its Complications xxx (2015) xxx–xxx

hyperthyroidism, and uncontrolled hypertension (systolic blood pressure N 180 mmHg). A total of 168 type 2 diabetic patients and 43 age-matched, non-diabetic control subjects participated in this study. Control subjects had been visiting the hospital for the treatment of hyperlipidemia and/or hypertension. Lipid levels and blood pressure were well controlled in these patients, and patients with underlying disease were excluded. A written informed consent was obtained from all patients. The participants were interviewed by a professional interviewer for approximately 30–60 min, and they answered questionnaires about the frequency of falls, hypoglycemia, the risk of falls, the activities of daily living (ADL), depressive symptoms, and cognition. The study was approved by the hospital ethics committee.

cemic symptoms with prompt recovery by self-administered intake of sugar or glucose, whereas severe hypoglycemia was defined as the occurrence of coma, convulsion, or inability of self-management and recovery from hypoglycemic symptoms (American Diabetes Association Workgroup on Hypoglycemia, 2005). The frequency of hypoglycemia that was self-reported by diabetic patients using the questionnaires correlated well with that judged by attending medical doctors in our previous study (r = 0.796, P b 0.001, n = 855) (Araki et al., 2012). Diabetic patients were divided into three groups according to the frequency of hypoglycemia: no hypoglycemia, hypoglycemia once or twice a year, and hypoglycemia ≧ three times a year. 2.6. Statistical analysis

2.2. Medical history and diabetic complications Medical history including diabetic complications and the number and types of medications were recorded in medical charts. Diabetic retinopathy was assessed by funduscopic examination on dilated pupils by experienced ophthalmologists using direct ophthalmoscopy. Findings were classified into four stages: no retinopathy, background retinopathy, pre-proliferative retinopathy, and proliferative retinopathy. According to the lowest urinary albumin-tocreatinine ratio (ACR; mg/g creatinine) in two or three successive urinalyses, nephropathy was classified into four stages. Diabetic neuropathy was defined as the loss of bilateral Achilles tendon reflexes, diminished vibration sensation, and/or neuropathic symptoms, such as the lowering of sense and thermal nociception, or a history of foot ulcers or gangrenes. Stroke, CHD, and peripheral vascular disease were clinically diagnosed as reported elsewhere (Araki et al., 2012). 2.3. Falls and fall risk A fall was defined as an unexpected event in which the person comes to rest on the ground, floor, or lower level. The frequency of falls in the past one year was investigated using the questionnaire about the number and type of falls (non-injurious or injurious falls, complicated with a head-injury or fractures). Multiple falls were defined as ≧ 2 falls a year. The risk of fall was assessed using the 21-item Fall Risk Index by Toba, Kikuchi, Iwata, and Kozaki (2009), which included physical, psychological, and environmental factors, and the total Fall Risk Index score was calculated. 2.4. Physical, psychological, cognitive function, and physical performance To assess ADL, depression, and cognition, the 13-item ADL score (Tokyo Metropolitan Institute of Gerontology Index of competence: TMIG index) (Shibata, Sugisawa, & Watanabe, 2001), the 15-item geriatric depression scale (GDS-15) (Sheikh & Yesavage, 1986), and the Mini-mental state examination (MMSE) (Folstein, Folstein, & McHugh, 1975) were used. Physical performance was assessed using the Timed Up and Go test (TUG test) (Nordin, Lindelèof, Rosendahl, Jensen, & Lundin-Olsson, 2008), the functional reach test as a dynamic balance test (Duncan, Weiner, Chandler, & Studenski, 1990) was conducted and grip power was also measured. 2.5. Assessment of hypoglycemia Hypoglycemia was defined as the presence of autonomic and neuroglycopenic symptoms of hypoglycemia, which recovered promptly (within 10 min) after the intake of glucose or sucrose. The frequency of mild or severe hypoglycemia was assessed using questionnaires (e.g., number of hypoglycemic episodes, number of comas or emergency hospital visits, or admissions due to hypoglycemia). Mild hypoglycemia was defined as the appearance of hypogly-

The clinical characteristics and possible risk factors for falls were compared between the diabetic and non-diabetic control groups, or between diabetic patients with and without any falls. The differences of continuous variables between the two groups were analyzed using the Student's t test or Mann–Whitney U-test, where appropriate. The difference of prevalence was analyzed using the Pearson's chi-square test. The linear trend between the frequency of hypoglycemia and falls was assessed using the Mantel–Haenszel linear-by-linear association chi-square test. To examine the independent determinants of falls, we performed multiple logistic regression analysis using the significant variables in univariate analysis (P b 0.05): age, sex, cognitive impairment (MMSE b 26), TUG score, GDS-15 scores, the Fall Risk Index, and the presence of hypoglycemia. We used the Hosmer–Lemeshow goodness-of-fit statistic, which is more precise than the traditional goodness-of-fit statistic used in logistic regression. Unadjusted and adjusted odds ratios for falls were estimated for each risk factor. All analyses were conducted using IBM SPSS Statistics 18 (Japan IBM, Tokyo), and P b 0.05 was considered statistically significant. Data were presented as mean ± standard deviation (SD) unless otherwise specified. 3. Results There were no significant differences in age, sex, or BMI between control and diabetic groups. Diabetic patients showed higher systolic blood pressure, lower ADL, and higher GDS-15 scores. In the TUG test, diabetic patients spent more time completing the test than control subjects (P b 0.001). Total scores of the Fall Risk Index were also significantly higher in diabetic patients than in control subjects (P b 0.001; Table 1). The prevalence of those who had a history of at least one episode of any type of fall over the past year was twice as high in diabetic patients as in control subjects (36.9% vs. 18.6%, P = 0.023). In diabetic patients, the mean HbA1c was 7.4 ± 0.8% (Table 1). The mean duration of diabetes was 18 ± 11 years. A total of 52.1% of patients were treated with sulfonylurea, 49.1% with biguanides, 23.7% with thiazolidinedione, 36.1% with α-glucosidase inhibitor, and 19.5% with insulin. When diabetic patients were exclusively analyzed, the HbA1c level in diabetic patients with falls was similar to that in patients without falls (7.4 ± 0.9% vs. 7.4 ± 0.8%). Further analysis revealed that there was no significant trend in the increase or decrease in the frequency of falls among the three HbA1c groups (b 6.5%, 6.5%–7.2%, N7.2%). Even if we divided subjects into two groups according to HbA1c levels (≦ 7.9% vs. ≧ 8.0%), similar results were obtained (29.4% vs. 37.7%, P = 0.602). The prevalence of any hypoglycemic episodes (once or more per year) was significantly higher (P = 0.036) in diabetic individuals with any fall (35.5%) than in those without them (20.8%; Table 2). The mean HbA1c level was not different between diabetic patients with and without any fall. Diabetic patients with falls had a significantly

Please cite this article as: Chiba, Y., et al., Risk factors associated with falls in elderly patients with type 2 diabetes, Journal of Diabetes and Its Complications (2015), http://dx.doi.org/10.1016/j.jdiacomp.2015.05.016

Y. Chiba et al. / Journal of Diabetes and Its Complications xxx (2015) xxx–xxx

a

Diabetic patients (n = 168)

P

75.2 ± 7.3 14 (32.6) 22.9 ± 2.9 124 ± 10 68 ± 8 5.5 ± 1.4 12.1 ± 1.6 2.9 ± 2.6 27.2 ± 3.5 9.6 ± 2.4 30.5 ± 7.8 15.5 ± 8.5 6.5 ± 3.5 8 (18.6) 4 (9.3)

76.2 ± 6.8 59 (35.1) 23.1 ± 3.3 128 ± 10 68 ± 7 7.4 ± 0.8 11.4 ± 2.2 3.9 ± 3.0 26.9 ± 2.9 12.0 ± 4.9 29.0 ± 7.2 13.2 ± 7.9 8.4 ± 3.3 62 (36.9) 22 (13.2)

0.404 0.753 0.683 0.027 0.983 b0.001 0.060 0.064 0.570 b0.001 0.231 0.107 b0.001 0.023 0.492

lower ADL score and MMSE and higher GDS-15 score than those without any fall. Furthermore, diabetic patients with falls also had a poor physical performance as assessed by the TUG test (Table 2). Total scores of the Fall Risk Index were also significantly higher in diabetic patients with falls compared with those without falls (P b 0.001). Any hypoglycemic episode was significantly associated with falls (twice or more per year) in diabetic patients (Tables 2 and 4; Fig. 1). When diabetic patients were divided into three groups according to the frequency of hypoglycemia (none, once or twice a year, and three or more times a year), the prevalence of falls increased as the frequency of hypoglycemia increased (Fig. 1). The frequency of hypoglycemia significantly correlated with that of falls (Spearman r = 0.215, P = 0.006). Moreover, the prevalence of falls in diabetic patients was not significantly correlated with the presence of peripheral neuropathy (35.9% vs. 33.8%, P = 0.784) and/or stroke (40.0% vs. 37.9%, P = 0.874). Similarly, there was no significant correlation between falls and use of insulin therapy or oral hypoglycemic agents (Table 2). The frequency of patients who used any oral hypoglycemic agent was similar in both groups (82.1% vs. 77.4%, P = 0.547; Table 2). The number of medications in diabetic patients with any fall (6.0 ± 3.3) was similar to that in patients without falls (5.5 ± 2.7) (Table 2). The use of antihypertensive drugs also did not affect falls (54.7% vs. 53.2%, P = 0.852). Furthermore, falls were not associated with polyphar-

Table 2 Demographic characteristics and fall risks in diabetic patients with/without falls. Diabetic patients

Age (years) Sex (men, %) BMI (kg/m2) HbA1c (%) ADL (TMIG index) GDS-15 MMSE Antihypertensive drugs (%) Oral hypoglycemic agents (%) Sulfonylurea (%) Glinide (%) Metformin (%) Pioglitazone (%) α-GI (%) Insulin (%) Number of medication Any hypoglycemia (%) TUG (sec) Functional reach (cm) Grip power (kg) Fall Risk Index

Without falls (n = 106)

With any fall (n = 62)

P

75.8 ± 6.6 36 (34.0) 22.8 ± 3.2 7.4 ± 0.8 11.7 ± 2.0 3.4 ± 2.8 27.3 ± 2.7 58 (54.7) 87 (82.1) 61 (57.5) 4 (3.8) 57 (53.8) 26 (24.5) 45 (42.5) 19 (17.9) 5.5 ± 2.7 22 (20.8) 11.0 ± 3.9 29.7 ± 7.0 14.1 ± 8.1 7.7 ± 3.2

76.9 ± 7.0 23 (37.1) 23.3 ± 3.4 7.4 ± 0.9 10.9 ± 2.5 4.7 ± 3.2 26.3 ± 3.1 33 (53.2) 48 (77.4) 28 (45.2) 6 (9.7) 29 (46.8) 14 (22.6) 17 (27.4) 15 (24.2) 6.0 ± 3.3 22 (35.5) 13.6 ± 5.9 27.8 ± 7.3 11.8 ± 7.4 9.9 ± 3.1

0.298 0.681 0.480 0.698 0.022 0.010 0.046 0.852 0.547 0.121 0.119 0.381 0.775 0.051 0.329 0.427 0.036 0.003 0.052 0.073 b0.001

60 50 40 30

50.0 20

52.4

32.0

10

0 Frequency of hypoglycemia/year

0 (n = 125)

1 or 2 (n = 22)

3 (n = 21)

b

Incidence of multiple falls (%)

Age (years) Sex (men, %) BMI (kg/m2) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) HbA1c (%) ADL (TMIG index) GDS-15 MMSE TUG (sec) Functional reach (cm) Grip power (kg) Fall Risk Index Any fall (per year, %) Multiple falls (per year, %)

Non-diabetic subjects (n = 43)

Incidence of any falls (%)

Table 1 Clinical characteristics, fall risks, and falls of diabetic patients and non-diabetic subjects.

3

35 30 25 20

33.3

15 10 5

0 Frequency of hypoglycemia/year

18.2 8.9 0 (n = 124)

1 or 2 (n = 22)

3 (n = 21)

Fig. 1. Relationship between the frequency of hypoglycemia and the incidence of falls for the past year in diabetic patients. (a) As the frequency of hypoglycemia (none, once or twice a year, or ≧ three times a year) increased, the incidence of falls for the past year tended to increase (the Mantel–Haenszel linear-by-linear chi-square = 4.603, df = 1, P = 0.032). (b) The incidence of multiple falls for the past one year significantly increased as the frequency of hypoglycemia increased (none, once or twice a year, or ≧ three times a year; the Mantel–Haenszel linear-by-linear chi-square = 9.767, df = 1, P = 0.002).

macy (number of medications N 5; 40% vs. 31%, P = 0.320) or the use of hypnotics (46% vs. 36%, P = 0.320). Multiple logistic regression analysis using six variables (age, sex, the presence of diabetes mellitus, the GDS-15 and TUG test scores, and the presence of hypoglycemia) revealed that the presence of hypoglycemia (OR 2.3, 95% CI: 1.1–5.0, P = 0.027) and the TUG test score (OR 1.1, 95% CI: 1.0–1.2, P = 0.021) was independently correlated with falls in all subjects. There were no significant correlations between the fall and other factors. On analyzing only diabetic patients, the presence of any level of hypoglycemia and the TUG test score was similarly correlated with falls (Table 3). When the Fall Risk Index score was added to the model, the presence of hypoglycemia, as well as the TUG score, still had borderline significance. In contrast, the presence of hypoglycemia, cognitive impairment (MMSE b 26), and the Fall Risk Index was a significant determinant for multiple falls in diabetic patients (the Hosmer–Lemeshow statistic: model of superiority = 186.963, accuracy rate of predicted value = 70.8%, P = 0.380). We did not find the effect of any interaction between hypoglycemia and insulin or oral hypoglycemic agents. This interaction even after multiple logistic regression analysis with the inclusion of factors such as stroke, coronary heart diseases, and peripheral neuropathy showed that hypoglycemia was an independent risk factor for multiple falls (OR 3.7, 95% CI: 1.1–12.3, P = 0.035). 4. Discussion In this study, elderly diabetic patients were twice as likely to have falls as control subjects (Table 1). Although the number of control subjects was small in this study, the rate of fall incidence had results

Please cite this article as: Chiba, Y., et al., Risk factors associated with falls in elderly patients with type 2 diabetes, Journal of Diabetes and Its Complications (2015), http://dx.doi.org/10.1016/j.jdiacomp.2015.05.016

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Table 3 Multiple logistic regression analysis of variables associated with falls in diabetic patients. Any fall

Age Sex MMSE b 26 TUG score GDS-15 score Fall Risk Index Any hypoglycemia

Multiple falls

OR (95% CI)

P

OR (95% CI)

P

0.98 0.68 1.29 1.07 1.03 1.16 2.05

0.711 0.277 0.532 0.110 0.704 0.019 0.075

1.01 0.50 3.63 0.94 1.02 1.20 3.62

0.903 0.199 0.020 0.331 0.811 0.039 0.018

(0.932–1.049) (0.322–1.384) (0.579–2.880) (0.984–1.172) (0.898–1.173) (1.026–1.318) (0.930–4.535)

(0.924–1.094) (0.176–1.436) (1.227–10.727) (0.835–1.063) (0.847–1.237) (1.010–1.425) (1.242–10.534)

Variables entered in the model: age, sex, cognitive impairment (MMSE b 26), TUG score, GDS-15 score, Fall Risk Index and presence of any hypoglycemia.

similar to those reported in a previous study of falls among community-dwelling elderly in Japan (Yasumura & Hasegawa, 2009). The result was consistent with the prospective cohort study of elder patients, showing that the fall incidence rate for the participants with and without diabetes mellitus was 78% and 30%, respectively (Maurer et al., 2005). Diabetes mellitus may be associated with an increased risk of falling in elderly patients (Roman de Mettelinge, Cambier, Calders, Van Den Noortgate, & Delbaere, 2013; Schwartz et al., 2002). Another study from the United Kingdom showed that approximately 40% of elderly diabetic patients report falling each year (Tilling, Darawil, & Britton, 2006). The multiple and well-recognized complications of long-standing diabetes mellitus include peripheral neuropathy, diabetic retinopathy, autonomic neuropathy, and hypoglycemia from inappropriate glycemic control, all of which can significantly contribute to the risks of falls through multiple mechanisms (Morley, 1999). Recently, Kachoo et al. (2015) showed that the risk of fall-related events increased 2-fold among elderly diabetic patients who experienced hypoglycemia. Our study indicated that in diabetic patients, the prevalence of falls increased as the frequency of hypoglycemia increased (Fig. 1). The results of this study showed that the occurrence of hypoglycemia may have led to falls in elderly patients with diabetes mellitus. Several mechanisms can explain how hypoglycemia induces falls. Cognitive impairments, such as deficits in attention and the slowing of psychomotor speed, which occurs during hypoglycemia and lasts for approximately 30 min after the recovery of hypoglycemia, would cause falls (Kodl & Seaquist, 2008). Hypoglycemia itself may induce a transient functional impairment of vascular autonomic nerves, which may cause orthostatic hypotension. Furthermore, frequent hypoglycemia may be associated with depressive symptoms in diabetic patients (Shao, Ahmad, Khutoryansky, Aagren, & Bouchard, 2013), which also lead to falls due to the lack of attention and cognition. In our study, higher depressive symptoms and cognitive impairment were associated with falls in diabetic patients (Tables 2 and 4). These results are consistent with the findings of several studies (Roman de Mettelinge et al., 2013; Whooley et al., 1999). Although diabetes is associated with geriatric syndromes including functional decline, cognitive impairment, depression, and falls in frail elderly patients, these symptoms are mutually related (Araki & Ito, 2009; Brown, Mangione, Saliba, & Sarkisian, 2003). Hypoglycemia may also impair psychological and cognitive function, which could lead to falls, resulting in a detrimental cycle. Although some studies have shown that lower HbA1c levels are associated with falls in diabetic patients (Nelson et al., 2007; Schwartz et al., 2008), there was no significant correlation between low HbA1c levels and the incidence of falling in the present study (Tables 2 and 4). The differences of results among studies are possibly due to the differences of subjects in terms of the quality of glycemic control and diabetes treatment. Silent hypoglycemia tends to occur more often in patients with a higher HbA1c and glycemic variability, as well

Table 4 Demographic characteristics and the risks of fall in diabetic patients with/without multiple falls. Diabetic patients

Age (years) Sex (men, %) BMI (kg/m2) HbA1c (%) ADL (TMIG index) GDS-15 MMSE Antihypertensive drugs (%) Any hypoglycemia (%) TUG test (sec) Functional reach (cm) Grip power (kg) Fall Risk Index

Without multiple falls (n = 145)

With multiple falls (n = 22)

P

76.0 ± 6.4 50 (34.5) 23.3 ± 3.3 7.4 ± 0.9 11.6 ± 1.9 3.7 ± 2.9 27.2 ± 2.6 79 (54.5) 33 (22.8) 11.8 ± 4.8 28.9 ± 7.9 13.6 ± 7.9 8.2 ± 3.3

77.1 ± 8.9 9 (40.9) 21.8 ± 3.1 7.3 ± 0.7 10.1 ± 3.4 4.9 ± 3.5 25.1 ± 3.9 11 (50.0) 11 (50.0) 12.7 ± 5.3 29.7 ± 7.0 11.3 ± 8.2 10.4 ± 3.1

0.461 0.557 0.059 0.471 0.060 0.090 0.019 0.694 0.007 0.468 0.634 0.204 0.005

as in those with lower HbA1c levels (Engler et al., 2011). In addition, variation in blood glucose does not affect HbA1c (Derr, Garrett, Stacy, & Saudek, 2003). Thus, hypoglycemia can occur in poor glycemic control with higher blood glucose variability. Therefore, HbA1c levels may not be a reliable indicator of hypoglycemia and the risk of falls. One of the reasons for the high frequency of falls in diabetic patients may be impaired balance and low muscle strength. Maurer et al. (2005) found that gait and balance were independent predictors of falls in a population of elderly diabetic patients in the nursing home. In the TUG test, diabetic patients spent more time completing the test than control subjects (Table 1), and the TUG test score was independently correlated with falls (Table 3). Furthermore, according to the Fall Risk Index, diabetic patients had remarkable problems concerning gait and stair climbing, possibly due to low muscle strength and impaired balance. Diabetic patients are more likely to have sarcopenia, which is defined as an accelerated loss of muscle mass and low muscle strength, or an impaired physical performance because of hyperglycemia, insulin resistance, diabetic neuropathy, and normal aging (Andersen, Nielsen, Mogensen, et al., 2004; Morley, Baumgartner, Roubenoff, Mayer, & Nair, 2001; Park et al., 2006; Wang & Hazuda, 2011). Thus, impaired balance and sarcopenia in patients with diabetes mellitus may lead to increased falls, frailty, and disability (Morley et al., 2001). Patients with diabetic neuropathy have reduced walking speed, cadence, and step length, particularly when walking on an irregular surface; they may have impaired peripheral sensation, reaction time, and balance (Menz, Lord, St George, & Fitzpatrick, 2004). However, in our study, there was no significant correlation between the presence of polyneuropathy and incidence of falls. The reason for the lack of correlation between neuropathy and falls may be due to a decrease in the specificity of the diagnosis of diabetic neuropathy, because aging normally causes decreases in the vibration sense or deep tendon reflex of lower limbs. Alternatively, a part of peripheral neuropathy in elderly diabetic patients may induce muscle atrophy as well as the impairment of physical performance of lower extremities (Menz et al., 2004; Strotmeyer et al., 2008; Wang & Hazuda, 2011). There are several limitations to our study. First, our study was retrospective and cross-sectional. A prospective study will be necessary to clarify the relationship between hypoglycemia and falls. To determine whether the prevention of hypoglycemia results in a decrease in fall episodes, further prospective intervention studies are also required. Second, hypoglycemia was based upon survey questionnaires regarding events occurring within the past one year; thus, exact blood glucose levels and the exact temporal relationship between hypoglycemia and fall events were unknown. Although it is unknown whether the hypoglycemia assessed by the questionnaire used in this study corresponds to that evaluated by the self-

Please cite this article as: Chiba, Y., et al., Risk factors associated with falls in elderly patients with type 2 diabetes, Journal of Diabetes and Its Complications (2015), http://dx.doi.org/10.1016/j.jdiacomp.2015.05.016

Y. Chiba et al. / Journal of Diabetes and Its Complications xxx (2015) xxx–xxx

monitoring blood glucose, the frequency of hypoglycemia assessed with questionnaire did increase after the six-year intervention by insulin therapy in another study (Araki & Ito, 2015). Furthermore, it is highly possible that a retrospective questionnaire will have recall bias. In particular, elderly patients with mild cognitive impairment might forget the episodes of hypoglycemia or falls that occurred during the year. Asymptomatic hypoglycemia could not be detected in our questionnaire, even if the patients used self-monitoring blood glucose systems. However, asymptomatic hypoglycemia is often seen in those with symptomatic hypoglycemia and may have some influence on falls. Third, comorbid conditions such as ischemic heart disease, dizziness, and vertigo may have affected falls. Hypoglycemia shows various symptoms, sometimes making it difficult to distinguish from the symptoms of other illnesses. However, in our previous study, there was no significant difference in the prevalence of hypoglycemia detected between physicians (judged from clinical symptoms) and patients (Araki et al., 2012). The Fall Risk Index, as a risk indication of comorbidity, did not affect the correlation between hypoglycemia and falls. Therefore, in this study, the influence of comorbidities seems to be small. In conclusion, the incidence and risks of falls increased in elderly diabetic patients. The presence of hypoglycemia, cognitive impairment, and high scores of Fall Risk Index was independently correlated with multiple falls in elderly type 2 diabetic patients. This study suggests that both avoidance of hypoglycemia and fall risk assessment are of great importance to prevent falls in elderly patients with diabetes mellitus.

Acknowledgments This study was supported by the Health and Labour Science Research Grant (H21-Chouju-Ordinal-005) and the Japan Foundation for Aging and Health. The authors would like to thank Enago (www.enago.jp) for the English language review.

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Please cite this article as: Chiba, Y., et al., Risk factors associated with falls in elderly patients with type 2 diabetes, Journal of Diabetes and Its Complications (2015), http://dx.doi.org/10.1016/j.jdiacomp.2015.05.016

Risk factors associated with falls in elderly patients with type 2 diabetes.

This study investigated risk factors of falls in elderly patients with type 2 diabetes mellitus...
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