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Loneliness Relates to Functional Mobility in Older Adults with Type 2 Diabetes: The Look AHEAD Study

Loneliness Relates to Functional Mobility in Older Adults with Type 2 Diabetes: The Look AHEAD Study Hindawi Journal of Aging Research Volume 2020, Article ID 7543702, 8 pages https://doi.org/10.1155/2020/7543702 Review Article Loneliness Relates to Functional Mobility in Older Adults with Type 2 Diabetes: The Look AHEAD Study 1 2 3 2 Jeanne M. McCaffery , Andrea Anderson, Mace Coday, Mark A. Espeland, 4 3 5 6 Amy A. Gorin, Karen C. Johnson, William C. Knowler, Candice A. Myers, 7 8 9 10 W. Jack Rejeski, Helmut O. Steinberg, Andrew Steptoe, and Rena R. Wing Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC, USA Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA InstituteforCollaborationonHealth,InterventionandPolicy,andPsychologicalSciences,UniversityofConnecticut,Storrs,CT, USA Diabetes Epidemiology and Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute for Diabetes, Digestive and Kidney Diseases, Phoenix, AZ, USA Pennington Biomedical Research Center Baton Rouge, Baton Rouge, LA, USA Department of Health and Exercise Science, Wake Forest School of Medicine, Winston-Salem, NC, USA Department of Endocrinology, University of Tennessee Health Science Center, Memphis, TN, USA Behavioural Science and Health Institute of Epidemiology & Health, University College London, London, UK Department of Psychiatry and Human Behavior, 8e Miriam Hospital and Alpert School of Medicine at Brown University, Providence, RI, USA Correspondence should be addressed to Jeanne M. McCaffery; Jeanne.mccaffery@uconn.edu Received 10 June 2020; Accepted 19 August 2020; Published 30 October 2020 Academic Editor: F. R. Ferraro Copyright © 2020 Jeanne M. McCaffery et al. %is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective. Little is known about the impact of loneliness on physical health among elderly individuals with diabetes. Here, we examined the relationship of loneliness with disability, objective physical function, and other health outcomes in older individuals with type 2 diabetes and overweight or obesity. Method. Data are drawn from the Look AHEAD study, a diverse cohort of individuals (ages 61–92) with overweight or obesity and type 2 diabetes measured 5–6 years after a 10-year weight loss ran- domized, controlled trial. Results. Loneliness scores were significantly associated with greater disability symptoms and slower 4- meter gait speed (ps< 0.01). Loneliness did not differ across treatment arms. Discussion. Overall, these results extend prior findings relating loneliness to disability and decreased mobility to older individuals with type 2 diabetes and overweight or obesity. status each increase risk for loneliness [2, 3]. Roughly, 1. Introduction 25–43% of adults over the age of 70 report being lonely [4]. Loneliness is a subjective state, reflecting a lack of desired Loneliness is a well-established correlate of mental closeness with friends, family, and loved ones. Compared health, quality of life [5–7], and early mortality in older with structural measures of social contacts, counting an adults [8–14]. Moreover, loneliness has previously been individual’s opportunities for interaction with other people, shown to relate to disability [15, 16] and impaired mobility loneliness assesses the function of social interactions in [17]. For example, loneliness predicted a faster rate of ob- allowing a person to feel connected to others [1]. Living jectively-measured motor decline, defined by motor func- alone, widowhood, poor health status, and poor functional tion and muscle strength, over five years of follow-up among 2 Journal of Aging Research 985 men and women, with a mean age of 80 [17]. Peri- reassessed at year 15 to continue to follow diabetes and ssinotto and colleagues [13] found that loneliness was related aging-related outcomes, including measuring loneliness for to greater difficulty with activities of daily living and mobility the first time. %e study enrolled 5,145 men and women, at six year follow-up among over 14,000 men and women aged 45–76 at baseline. %e present study is cross-sectional over the age of 60 in the Health and Retirement Study. and derives variables from 15 year follow-up when partic- Higher levels of loneliness also predicted frailty as defined by ipants had a mean age of 75 (range: 61–92). All Look the Fried Formula at 4 year follow-up among 2,817 indi- AHEAD participants who were attending clinical visits were viduals over 60 years of age from the English Longitudinal included (n � 3187). Look AHEAD participants who were Study of Aging [15]. Interestingly, Hoogendijk and col- followed only through telephone interviews (n � 300) were leagues [18] reported that frailty increased the risk for excluded because loneliness was not queried. loneliness over 3 years, suggesting that the relationship between loneliness and physical function may be bidirec- 2.2. Study Interventions. Eligible patients were randomly tional [18]. assigned to participate in ILI (intervention group) or DSE Little is known about how loneliness relates to health (comparison group), with stratification according to clinical status among older individuals with type 2 diabetes. In the United States, 25% of individuals over the age of 65 have type site. Curricula for the two study groups were developed centrally and have been described in detail previously 2 diabetes [19] increasing the risk for early mortality, car- [27, 28]. diovascular disease, renal disease, dementia, functional impairment, depression, and vision impairment [20]. Al- though less stringent treatment goals can be recommended 2.3. Intensive Lifestyle Intervention (ILI). %e ILI included for elderly individuals, the need for diabetes self-manage- calorie restriction, low-fat diet, and increased physical activity ment remains including treatment adherence, nutrition, and and was designed to induce at least a 7% weight loss at year 1 exercise [21]. Social support improves diabetes self-man- and to maintain this weight loss in subsequent years. ILI agement, medication adherence, diet change, active lifestyles participants were assigned a calorie goal (1200–1800 kcal/d and, in some cases, glycemic control [22]. Conversely, based on initial weight), with less than 30% of total calories loneliness is associated with less physical activity [23, 24] and from fat (<10% from saturated fat) and a minimum of 15% of poorer sleep quality [25, 26]. As such, it is plausible that total calories from protein. %e exercise goal was at least loneliness may relate to health outcomes among elderly 175 minutes of physical activity per week, using activities individuals with type 2 diabetes but these associations have similar in intensity to brisk walking. ILI participants were seen not been established. for 3 groups and one individual session per month for the first Look AHEAD was a randomized controlled trial 6 months and 2 group, one individual session per month for designed to determine whether 10 years of intensive lifestyle the next 6 months, and at least monthly through year 10. ILI intervention (ILI), comprised of calorie restriction and was effective in inducing and sustaining weight losses relative physical activity promotion to achieve weight loss, improves to the control condition throughout follow-up [28]. health outcomes among older individuals with type 2 dia- betes and overweight or obesity, relative to a Diabetes Support and Education (DSE) control group. %e cohort was 2.4. Diabetes Support and Education (DSE). DSE featured reassessed for aging-related outcomes at 15-year follow-up, three group sessions per year focused on diet, exercise, and including loneliness measured for the first time. %e goal of social support during years 1 through 4. In subsequent years, this paper is to characterize the prevalence of loneliness the frequency was reduced to one session annually. among individuals with type 2 diabetes and overweight or obesity in the Look AHEAD cohort and to determine cross- sectional associations of loneliness score with self-reported 3. Measures disability and objective mobility and other health indicators, including HbA1c, quality of life, and depressive symptoms. 3.1. Loneliness. Loneliness was measured using the UCLA It is hypothesized that loneliness will relate to (1) greater Brief Loneliness Scale [29]. %e scale contains three ques- disability and decreased mobility and physical function, as tions: “How often do you feel that you lack companion- defined by the 400 m walk, grip strength, and the Short ship?”, “How often do you feel left out?”, and “How often do Physical Performance Battery and (2) higher HbA1c and you feel isolated from others?” Each item has the response depressive symptoms and lower quality of life. choices of “Hardly ever,” “Some of the time,” and “Often,” assigned scores 0, 1, and 2 respectively. %ese scores for each of the items are summed to give a total score. %e prevalence 2. Methods of loneliness has also been defined as reporting “Some of the 2.1. Research Design. Look AHEAD is a randomized, con- time” or “Often” relative to “Hardly ever” for at least one of trolled trial designed to test whether 10 years of ILI, com- the three questions: “How often do you feel that you lack bining calorie restriction and physical activity to produce companionship?”, “How often do you feel left out?” and weight loss, improves health outcomes among individuals “How often do you feel isolated from others?” [13]. %e with type 2 diabetes and overweight or obesity, relative to UCLA Brief Loneliness Scale was shown to have a strong DSE [27, 28] (see Supplementary File 2). %e cohort was correlation with the full UCLA Loneliness Scale (r � 0.82) Journal of Aging Research 3 scores of 0–3 based on increasing frequency and summing and to have reasonable internal consistency (Cronbach’s α � 0.72) [29]. the scores (range: 0–27). %e PHQ-9 has strong internal consistency (α � 0.89) and test-retest reliability (r � 0.84) in clinical samples [33]. %e PHQ-9 does not include a lone- 3.2. Disability and Physical Function liness item. 3.2.1. Pepper Assessment Tool for Disability (PAT-D). %e PAT-D is an 18-item self-report questionnaire designed to 3.3.2. Antidepressant Medications. Participants brought all assess disability in older adults. Participants are asked to rate: prescription medications to their annual clinic assessment “How much difficulty, if any, do you have with each of these visits, and these medications (but not the dosages) were activities? %ink about the past month. How hard was it to recorded by study staff. Antidepressant medications were do the activity because of your health?” Items include identified using the Food and Drug Administration classi- questions such as “Moving in and out of bed” and “Dressing fication system. yourself.” Responses range from “Usually did with no dif- ficulty” (1) to “Unable to do” (5) with the possibility of 3.3.3. Quality of Life. Quality of life was assessed using the endorsing “Usually did not do for other reasons.” Scores are SF-36 General Health questionnaire [34]. %e questionnaire averaged across the 18 items. %e PAT-D has shown strong asks participants: “In general, would you say your health internal consistency (α � 0.82) and test-retest reliability is. . .” with responses ranging from Excellent (1) to Poor (5) (r> 0.70). on a 1–5 scale. Lower values indicate better general health. 3.2.2. Physical Function Tests. Objective physical function 3.3.4.HbA1candDiabetesMedications. HbA1c was assayed was assessed in the full cohort at an average of 15–16 year from fasting blood samples. Six major classes of diabetes follow-up. %e Short Physical Performance Battery Ex- medications were categorized from the Food and Drug panded (SPPBexp) [30], a modestly expanded form of the Administration classification system and were used as Short Physical Performance Battery [31] designed to min- covariates in analyses of HbA1c. imize ceiling effects of the SPPB when used in well-func- tioning populations, was administered to assess lower extremity physical function. %e SPPB consists of standing 3.4. Statistical Analysis. Primary analyses were conducted balance tasks (side-by-side, semi- and full-tandem stands for using linear or logistic regression depending on the out- 10 seconds each), a 4 m walk to assess usual gait speed and come. Model 1 tested the association of loneliness, age, sex, time to complete five repeated chair stands. %e SPPBexp race, and ethnicity with the function- and health-related increased the holding time of the standing balance tasks to variables. Model 2 added depressive symptoms and anti- 30 seconds and added a single leg stand. %e SPPBexp depressant medications to determine whether loneliness component scores are calculated as the ratio of observed relates to the other variables independent of correlated performance to the best possible performance and summed constructs also known to relate to health outcomes. For the to provide a continuous score ranging from 0 to 3, with relationship of loneliness to HbA1c, the six major categories higher scores indicative of better performance. Usual of diabetes medications were added as covariates to Model 2. walking speed over 20 m and walking endurance over 400 m Treatment arm was added in Model 3 to determine whether were measured [32]. %e course was 20 m long and marked loneliness differs by ILI. by cones at each end. Participants were instructed to walk at PHQ-9 and PAT-D scales are extremely skewed, even their usual pace, and time to complete the first 20 m and the after log transformation, and thus were dichotomized at longer 400 m was recorded. Grip strength (kg) was measured their lowest value vs anything else. twice in each hand using an isometric Hydraulic Hand Dynamometer (Jamar, Bolingbrook, IL). %e maximum 4. Results force from two trials for the stronger hand was used in the 4.1. Descriptive Statistics. Descriptive statistics for baseline analyses. and the Look AHEAD E visit (15-year follow-up) are pre- sented in Table 1. %e balance afforded by the original 3.3. Other Health Indicators randomization was maintained at the 15-year visit: no differences in baseline age, sex, race, or Hispanic ethnicity 3.3.1. Personal Health Questionnaire-9 (PHQ-9). %e PHQ- were observed. However, several health indices continued to 9 is a self-administered questionnaire assessing depressed show intervention effects, including lower BMI (32.9 vs 33.6; mood and depression severity [33]. %e questionnaire asks p � 0.002), faster gait speed (4.85 vs 5.00 seconds; p � 0.01), “How often, over the past two weeks, have you been and less insulin use (43.4% vs 49.5%; p � 0.0009) in the ILI bothered by any of the following problems?” for nine compared with DSE groups. No differences in loneliness by questions, including “Little interest or pleasure in doing Look AHEAD treatment arm were observed (p � 0.11). things” and “Feeling down, depressed, or hopeless.” Re- sponse options include “Not at all,” “Several days,” “More than half of the days,” and “Nearly every day.” Depressed 4.2. Prevalence of Loneliness. %irty-eight percent of the mood severity was calculated by assigning response options Look AHEAD samples reported being lonely as defined by 4 Journal of Aging Research Table 1: Characteristics of participants with nonmissing loneliness scale at the Look AHEAD-E visit. Intervention arm Nonmissing Overall p value DSE ILI N 3190 1553 1634 Baseline characteristics Age 3190 58.3 (6.4) 58.3 (6.4) 58.2 (6.3) 0.7042 BMI 3190 35.9 (6.0) 36.0 (5.8) 35.7 (6.1) 0.1338 Gender Male 3190 1214 (38.1%) 581 (37.4%) 633 (38.7%) 0.4756 Female 1976 (61.9%) 973 (62.6%) 1003 (61.4%) Race/ethnicity White 1939 (60.8%) 950 (61.1%) 989 (60.5%) Black 3190 524 (16.4%) 260 (16.7%) 264 (16.2%) 0.6896 Hispanic 440 (13.8%) 203 (13.1%) 237 (14.5%) Others 287 (9.0%) 142 (9.1%) 145 (8.9%) LA-E visit Age 3190 72.7 (6.2) 72.7 (6.3) 72.7 (6.1) 0.7424 BMI 3019 33.2 (6.2) 33.6 (6.2) 32.9 (6.1) 0.0012 HbA1c% 2665 7.5 (1.5) 7.5 (1.5) 7.5 (1.4) 0.5779 PHQ-9 3052 2.7 (3.3) 2.8 (3.4) 2.6 (3.2) 0.1786 PHQ-9 � 0 3052 937 (30.7%) 458 (30.8%) 479 (30.6%) 0.9079 SF-36 general health 3156 2.9 (0.8) 2.9 (0.8) 2.9 (0.8) 0.4558 PAT-D 3157 1.5 (0.5) 1.5 (0.5) 1.5 (0.5) 0.5800 PAT-D � 1 3157 419 (13.3%) 212 (13.8%) 207 (12.8%) 0.4165 400 m walk time (min) 2632 6.7 (1.9) 6.8 (2.0) 6.7 (1.9) 0.6073 Gait speed test (sec) 2949 4.93 (1.67) 5.00 (1.71) 4.85 (1.62) 0.0168 Grip strength (right hand) 2702 23.9 (9.4) 23.8 (9.5) 24.0 (9.3) 0.5225 Taking antidepressants 2822 699 (24.8%) 337 (24.5%) 362 (25.0%) 0.7546 Taking any diabetes med 3067 2814 (91.8%) 1380 (92.3%) 1434 (91.2%) 0.2744 Biguanide 2967 2063 (69.5%) 1008 (69.5%) 1055 (69.6%) 0.9868 Insulin 2894 1344 (46.4%) 704 (49.5%) 640 (43.5%) 0.0010 Sulfonylurea 2863 979 (34.2%) 490 (35.1%) 489 (33.4%) 0.3460 TZD 2758 198 (7.2%) 94 (7.0%) 104 (7.4%) 0.6900 Loneliness 3190 3.86 (1.38) 3.90 (1.42) 3.82 (1.34) 0.1164 Values are given as mean (SD) or N (%) endorsing “Sometimes” to at least on the three questions on Loneliness did not correlate with the 400-meter walk test the UCLA Brief Loneliness Survey. Nine percent reported speed (β � 0.03± 0.03; p � 0.2375). “Often” for at least one question. After further adjustment for depression symptoms and antidepressant medication use (Table 2, Model 2), greater loneliness continued to significantly relate to higher Pepper 4.3. Differences in Loneliness Scores by Demographics and Disability Test scores (OR � 1.24; p � 0.0018) and slower gait BMI. As seen in Supplementary Table 1, levels of loneliness (β � 0.10± 0.03; p � 0.0003), but the association with grip differed meaningfully by demographics and BMI. %e mean strength was reduced to nonsignificance (β � −0.17± 0.12; loneliness score was higher in women compared to men p � 0.1592). Again, these associations were not substantially (p< 0.0001), individuals of Black, Hispanic, or other races and altered by statistical control for treatment arm (Table 2, ethnicities compared to whites (p � 0.0001), individuals with Model 3). less formal education (p< 0.0001), and individuals who have a 2 2 BMI≥ 40 kg/m at baseline (p � 0.02). A BMI≥ 40 kg/m at 15 year follow-up also was strongly related to loneliness 4.5. Loneliness, Depressive Symptoms, Antidepressant Medi- (p< 0.0001), but no differences in loneliness by age were cations,andQualityofLife. In models adjusting for age, sex, observed at 15 year follow-up (p � 0.38). race, and ethnicity (Table 2, Model 1), greater loneliness was significantly related to higher PHQ-9 scores (OR � 1.89; p< 0.0001) and a greater likelihood of taking antidepressant 4.4.Loneliness,Disability,andMobility. In models adjusting medications (OR � 1.32; p< 0.0001). After further adjust- for age, sex, race, and ethnicity (Table 2, Model 1), greater ment for antidepressant medication use (Table 2, Model 2), loneliness was significantly related to greater self-report of greater loneliness continued to relate to higher PHQ-9 disability on the Pepper Disability Test (OR � 1.47; scores (OR � 1.75; p< 0.0001). Similarly, after controlling p< 0.0001), slower gait speed (β � 0.19± 0.02; p< 0.0001), for PHQ-9 scores, greater loneliness continued to relate to and weaker hand grip (β � −0.39± 0.10; p< 0.0001). antidepressant use (OR � 1.12; p< 0.0001). %ese Journal of Aging Research 5 Table 2: Adjusted associations with loneliness. Model 1 Model 2 Model 3 Outcome Beta SE p value Beta SE p value Beta SE p value Gait speed test (seconds) 0.192 0.022 <0.0001 0.097 0.026 0.0002 0.096 0.026 0.0003 Grip strength (right hand) −0.382 0.097 <0.0001 −0.170 0.117 0.1471 −0.168 0.118 0.1530 400 m walk time 0.034 0.029 0.2451 0.038 0.035 0.2759 0.037 0.035 0.2839 SF-36 general health 0.140 0.011 <0.0001 0.035 0.012 0.0057 0.035 0.013 0.0058 HbA1c% 0.030 0.020 0.1372 0.009 0.023 0.6868 0.010 0.023 0.6632 OR 95% CI p value OR 95% CI p value OR 95% CI p value PAT-D> 1 1.470 1.313–1.645 <0.0001 1.243 1.085–1.424 0.0017 1.245 1.087–0.427 0.0016 PHQ-9> 0 1.897 1.723–2.088 <0.0001 1.752 1.585–1.938 <0.0001 1.754 1.586–1.939 <0.0001 Taking antidepressants 1.319 1.242–1.401 <0.0001 1.126 1.048–1.211 0.0013 1.127 1.048–1.211 0.0012 Note. Model 1: adjusts for age, sex, and race/ethnicity. Model 2: Model 1 plus depressive symptoms (PHQ-9) and antidepressant medication use. Also includes major diabetes med categories for HbA1c outcome (biguanide, insulin, sulfonylurea, and TZD) PHQ-9 outcome does not adjust for depressive symptoms. Taking antidepressants outcome does not adjust for antidepressant medication use. Model 3: Model 2 plus treatment arm. associations were not substantially altered by statistical quality of life after similar adjustment. %ese results identify control for treatment arm (Table 2, Model 3). loneliness as an important correlate of physical and mental In models adjusting for age, sex, race, and ethnicity health among aging individuals with an elevated body mass (Table 2, Model 1), greater loneliness was significantly re- index and type 2 diabetes. lated to lower self-rated general health on the SF-36 After adjustment for demographic variables, loneliness (β � 0.14± 0.01; p< 0.0001), and this association remained also correlated with a weaker hand grip but the association significant after controlling for depressive symptoms and weakened to nonsignificance after further adjustment for antidepressant medication use (β � 0.03± 0.01; p � 0.0063) depressive symptoms and use of antidepressant medications, (Table 2, Model 2). indicating that loneliness is not independently related to hand grip strength in this study. Loneliness did not sig- nificantly relate to HbA1c or the 400-meter walk test in any 4.6.LonelinessandHbA1c. Loneliness did not correlate with of the models. HbA1c in models adjusted for age, sex, race, and ethnicity %e prevalence of loneliness was similar to prior research (β � 0.03± 0.02; p � 0.1297), nor with further adjustment for in elderly individuals. Roughly 38% of these individuals with depressive symptoms, antidepressant medications, glucose- type 2 diabetes and obesity or overweight reported loneliness lowering medication, or treatment arm. at least some of the time, and 9% endorsed experiencing at least one of the loneliness questions often. In the most direct comparison, Perissinotto and colleagues used the UCLA 4.7. Interaction with Treatment Arm. Treatment arm inter- Brief Loneliness Scale (as was used in this paper) to estimate acted with loneliness in its association with two mobility prevalence of loneliness in the Health and Retirement Study, measures: 400-meter walk test (p � 0.03) and gait speed including noninstitutionalized individuals over the age of 65 (p � 0.03; Table 3). In each case, physical function was [13]. Forty-three percent endorsed loneliness on one of the similar across the spectrum of loneliness scores in the ILI, questions at least some of the time, and 13% reported feeling whereas higher loneliness was related to poorer physical lonely often, suggesting that the prevalence of loneliness in function in DSE. Supplementary Figures 1(a) and 1(b) il- th Look AHEAD is roughly comparable with the U.S. pop- lustrate the interactions with loneliness depicted at the 10 th ulation over the age of 65. (loneliness � 3) and 90 (loneliness � 6) percentiles of Levels of loneliness did not differ by randomized loneliness score. treatment arm. %is is likely due to the measurement of %ere was also an interaction of loneliness and treatment loneliness 15 years after the initiation of the intervention, arm in their associations with HbA1c (p � 0.04, Table 3). In and 5 years following the end of the intervention. More those with lower loneliness scores, there was no differential research is needed to determine the impact of lifestyle in- effect between treatment arms. However, in those with tervention for weight loss on loneliness, particularly in in- higher loneliness scores, HbA1c was lower in the ILI dividuals with BMI≥ 40, who showed an increased compared to the DSE (Supplementary Figure 1(c)). loneliness scores both at baseline and 15 year follow-up. Loneliness also appeared to moderate the impact of ILI 5. Discussion and DSE on mobility. %e interaction indicated that the In this sample of older individuals who have type 2 diabetes long-term effect of ILI on gait speed and the 400 m walk test and overweight or obesity, loneliness was associated with did not differ by loneliness. However, in DSE, loneliness higher disability scores and slower gait speed after statistical related to poorer outcomes for gait speed and the 400 m walk adjustment for several potential confounders. Loneliness test, leading to treatment arm by loneliness interactions. %is was also associated with higher depressive symptoms and suggests that ILI benefited mobility regardless of loneliness antidepressant medication use and poorer health-related level, whereas DSE predicted a lesser overall benefit and the 6 Journal of Aging Research Table 3: Exploring interactions with loneliness. It is important to note that the present study did not measure social isolation, a related but distinct measure of the Loneliness by treatment arm Outcome structure of social contacts. Social isolation also predicts (p value) aging-related outcomes [9, 12]. Indeed, several research Gait speed test (seconds) 0.0325 studies have compared the impact of loneliness to social Grip strength (right hand) 0.0568 isolation to determine whether the perception or structure of 400 m walk time 0.0253 social contacts has a greater impact on health, but research HbA1c% 0.0441 remains mixed [1, 6, 9, 15, 16, 23, 35]. It is also plausible that SF-36 general health 0.2164 loneliness and social isolation have synergistic effects PAT-D> 1 0.1308 wherein those with both conditions are at the greatest health PHQ-9> 0 0.2819 risk [36]. Future research in Look AHEAD should incor- Taking antidepressants 0.8536 porate a measure of social isolation, in addition to loneliness, to determine the relative contributions of each and the potential for compounding risks. benefit varied by loneliness. As DSE had minimal inter- Given the health risks, it is encouraging that interven- tions are being tested to reduce loneliness in the elderly. For vention, it is plausible that the relationship of loneliness to mobility in DSE is reflective of prior reports of associations example, Silver Sneakers, a gym membership and exercise with health outcome in more general populations, e.g., classes, was shown to increase physical activity and to reduce [15–17]. However, the impact of ILI on mobility may have social isolation and loneliness compared to matched controls blunted relationships with loneliness. [37]. In addition, a pilot, m-Health intervention targeting It further appeared that ILI was more effective in maladaptive cognitions in elderly individuals who are ex- reducing HbA1c compared with DSE among individuals periencing loneliness reduced these symptoms over three months [38]. with higher loneliness, whereas there was little difference by treatment arm among those with lower loneliness Although this study had several strengths, including an aging sample with type 2 diabetes, a large sample size, and levels. It is plausible that ILI may have been more effective among individuals with higher loneliness scores than objective measures of physical function, it is important to DSE due to the differential contacts with providers and note limitations. First, as this study was cross-sectional, the other participants in ILI. However, it should be recog- direction of association cannot be determined. Indeed, nized that the interaction analyses were exploratory and prior research suggests that the associations of loneliness not hypothesis driven. with depression and disability may be bidirectional [7, 18]. Taken together, these findings from a sample of older Future, longitudinal research will be needed to resolve participants who have type 2 diabetes and overweight or directionality in this cohort. In addition, the loneliness obesity share many similarities to the prior literature in- questionnaire was only included in the clinic questionnaire, which excluded 9.4% of participants who completed tele- volving older people without diabetes. Specifically, we find loneliness to relate to disability scores, objective gait speed, phone interviews but may have had more difficulty at- tending visits in the clinic. Neither social isolation nor depressive symptoms and use of antidepressant medications, and health-related quality of life, consistent with prior re- contemporaneous socioeconomic status was measured in ports [5, 7, 13, 15–18]. In contrast, we did not support prior Look AHEAD and may serve as confounders of the rela- studies finding relationships of loneliness with glycemic tionship between loneliness and the health outcomes. control. Given that diabetes impacts one in four elderly Lastly, although we did not see evidence for differential loss adults in the United States, requires a complicated self- of follow-up between treatment groups, we cannot rule out management regimen, and portends an increased burden that this may have introduced bias in differences and associations. from multiple diseases, it is critical to identify factors that may further compound disease risk. Overall, this study demonstrates that loneliness relates to greater disability, slower gait speed, depressive symptoms, One challenge of the literature relating loneliness to health outcomes is the variety of different scales used. Meta- antidepressant medication use, and poorer quality of life among older individuals who have type 2 diabetes and are analysis and reviews, e.g., [1, 4], identify numerous scales designed to characterize loneliness, with some scales overweight or obese. Future longitudinal research needs to showing overlap with structural measures of social con- address questions such as the potential for bidirectional nection. Some of the prior research has even relied on a relationships with loneliness and the longer-term impacts on single question to index loneliness. We used the UCLA Brief health outcomes. Loneliness Scale (three items). %is scale shows a strong correspondence with the original, 20-item questionnaire Data Availability [29] and has previously been demonstrated to relate to behavioral and physical outcomes, including depression [7], All Look AHEAD data will be made available through the physical function [16], and mortality [9], among other National Institute of Diabetes, Digestive, and Kidney Disease outcomes. %us, the scale was a reasonable choice to rep- data repository within two years in accordance with the resent the health impacts of loneliness. policy of the Look AHEAD clinical trial. Journal of Aging Research 7 between loneliness score and treatment arm in relation to Disclosure th 400 meter walk time. Interaction illustrated using the 10 th %e opinions expressed in this paper are those of the authors (loneliness � 3) and 90 (loneliness � 6) percentiles for the and do not necessarily reflect the views of the NIH or other loneliness score. Supplementary Figure 1(b): interaction funding sources. between loneliness score and treatment arm in relation to gait speed. Interaction illustrated using the th th 10 (loneliness � 3) and 90 (loneliness � 6) percentiles for Conflicts of Interest the loneliness score. Supplementary Figure 1(c): interaction All authors report no conflicts of interest. between loneliness score and treatment arm in relation to th hemoglobin A1c. Interaction illustrated using the 10 th (loneliness � 3) and 90 (loneliness � 6) percentiles for the Acknowledgments loneliness score. (Supplementary Materials) %is study was funded by the National Institutes of Health through cooperative agreements with the National Institute of References Diabetes and Digestive and Kidney Diseases (DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, [1] N. Leigh-Hunt, D. Bagguley, K. Bash et al., “An overview of DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, systematic reviews on the public health consequences of social isolation and loneliness,” PublicHealth, vol. 152, pp. 157–171, DK57008, DK57135, and DK56992). Additional funding was provided by the National Heart, Lung, and Blood Institute; [2] N. Savikko, P. Routasalo, R. S. Tilvis, T. E. Strandberg, and National Institute of Nursing Research; National Center on K. H. Pitkal ¨ a, ¨ “Predictors and subjective causes of loneliness Minority Health and Health Disparities; NIH Office of Re- in an aged population,” Archives of Gerontology and Geri- search on Women’s Health; and the Centers for Disease atrics, vol. 41, no. 3, pp. 223–233, 2005. Control and Prevention. %is research was supported in part by [3] J. Cohen-Mansfield, H. Hazan, Y. Lerman, and V. Shalom, the Intramural Research Program of the National Institute of “Correlates and predictors of loneliness in older-adults: a Diabetes and Digestive and Kidney Diseases. %e Indian Health review of quantitative results informed by qualitative in- Service (IHS) provided personnel, medical oversight, and fa- sights,” International Psychogeriatrics, vol. 28, no. 4, cilities. Additional support was received from the Johns pp. 557–576, 2016. Hopkins Medical Institutions Bayview General Clinical Re- [4] A. D. Ong, B. N. Uchino, and E. Wethington, “Loneliness and health in older adults: a mini-review and synthesis,” Geron- search Center (M01RR02719); the Massachusetts General tology, vol. 62, no. 4, pp. 443–449, 2016. Hospital Mallinckrodt General Clinical Research Center; the [5] M. E. Beutel, “Loneliness in the general population: preva- Massachusetts Institute of Technology General Clinical Re- lence, determinants and relations to mental health,” BMC search Center (M01RR01066); the Harvard Clinical and Psychiatry, vol. 17, no. 1, p. 97, 2017. Translational Science Center (RR025758-04); the University of [6] J. Golden, R. M. Conroy, I. Bruce et al., “Loneliness, social Colorado Health Sciences Center General Clinical Research support networks, mood and wellbeing in community- Center (M01RR00051); the Clinical Nutrition Research Unit dwelling elderly,” International Journal of Geriatric Psychia- (P30 DK48520); the University of Tennessee at Memphis try, vol. 24, no. 7, pp. 694–700, 2009. General Clinical Research Center (M01RR0021140); the Uni- [7] J. T. Cacioppo, M. E. Hughes, L. J. Waite, L. C. Hawkley, and versity of Pittsburgh General Clinical Research Center (GCRC) R. 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Wardle, “Social General Clinical Research Center (M01RR01346). %e fol- isolation, loneliness, and all-cause mortality in older men and lowing organizations have committed to make major contri- women,” Proceedings of the National Academy of Sciences, butions to Look AHEAD: FedEx Corporation; Health vol. 110, no. 15, pp. 5797–5801, 2013. Management Resources; LifeScan, Inc., Johnson and Johnson [10] T. J. Holwerda, A. T. F. Beekman, D. J. H. Deeg et al., “In- Company; OPTIFAST of Nestle HealthCare Nutrition, Inc.; creased risk of mortality associated with social isolation in Hoffmann-La Roche Inc.; Abbott Nutrition; and Slim-Fast older men: only when feeling lonely? Results from the Amsterdam Study of the Elderly (AMSTEL),” Psychological Brand of Unilever North America. Some of the information Medicine, vol. 42, no. 4, pp. 843–853, 2012. contained herein was derived from data provided by the [11] R. S. 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A. %isted, and J. T. Cacioppo, “Loneliness predicts reduced physical activity: cross-sectional & longi- tudinal analyses,” Health Psychology, vol. 28, no. 3, pp. 354–363, 2009. [25] B. Yu, A. Steptoe, K. Niu, P.-W. Ku, and L.-J. Chen, “Pro- spective associations of social isolation and loneliness with poor sleep quality in older adults,” Quality of Life Research, vol. 27, no. 3, pp. 683–691, 2018. [26] L. M. Kurina, K. L. Knutson, L. C. Hawkley, J. T. Cacioppo, D. S. Lauderdale, and C. Ober, “Loneliness is associated with sleep fragmentation in a communal society,” Sleep, vol. 34, no. 11, pp. 1519–1526, 2011. [27] D. H. Ryan, M. A. Espeland, G. D. Foster et al., “Look AHEAD (Action for Health in Diabetes): design and methods for a clinical trial of weight loss for the prevention of cardiovascular disease in type 2 diabetes,” Controlled Clinical Trials, vol. 24, no. 5, pp. 610–628, 2003. [28] %e Look AHEAD Research Group, “Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes,” New En- gland Journal of Medicine, vol. 369, pp. 145–154, 2013. [29] M. E. Hughes, L. J. Waite, L. C. Hawkley, and J. T. Cacioppo, “A short scale for measuring loneliness in large surveys,” Research on Aging, vol. 26, no. 6, pp. 655–672, 2004. [30] J. M. Guralnik, E. M. Simonsick, L. Ferrucci et al., “A short physical performance battery assessing lower extremity function: association with self-reported disability and http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Aging Research Hindawi Publishing Corporation

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Hindawi Journal of Aging Research Volume 2020, Article ID 7543702, 8 pages https://doi.org/10.1155/2020/7543702 Review Article Loneliness Relates to Functional Mobility in Older Adults with Type 2 Diabetes: The Look AHEAD Study 1 2 3 2 Jeanne M. McCaffery , Andrea Anderson, Mace Coday, Mark A. Espeland, 4 3 5 6 Amy A. Gorin, Karen C. Johnson, William C. Knowler, Candice A. Myers, 7 8 9 10 W. Jack Rejeski, Helmut O. Steinberg, Andrew Steptoe, and Rena R. Wing Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC, USA Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA InstituteforCollaborationonHealth,InterventionandPolicy,andPsychologicalSciences,UniversityofConnecticut,Storrs,CT, USA Diabetes Epidemiology and Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute for Diabetes, Digestive and Kidney Diseases, Phoenix, AZ, USA Pennington Biomedical Research Center Baton Rouge, Baton Rouge, LA, USA Department of Health and Exercise Science, Wake Forest School of Medicine, Winston-Salem, NC, USA Department of Endocrinology, University of Tennessee Health Science Center, Memphis, TN, USA Behavioural Science and Health Institute of Epidemiology & Health, University College London, London, UK Department of Psychiatry and Human Behavior, 8e Miriam Hospital and Alpert School of Medicine at Brown University, Providence, RI, USA Correspondence should be addressed to Jeanne M. McCaffery; Jeanne.mccaffery@uconn.edu Received 10 June 2020; Accepted 19 August 2020; Published 30 October 2020 Academic Editor: F. R. Ferraro Copyright © 2020 Jeanne M. McCaffery et al. %is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective. Little is known about the impact of loneliness on physical health among elderly individuals with diabetes. Here, we examined the relationship of loneliness with disability, objective physical function, and other health outcomes in older individuals with type 2 diabetes and overweight or obesity. Method. Data are drawn from the Look AHEAD study, a diverse cohort of individuals (ages 61–92) with overweight or obesity and type 2 diabetes measured 5–6 years after a 10-year weight loss ran- domized, controlled trial. Results. Loneliness scores were significantly associated with greater disability symptoms and slower 4- meter gait speed (ps< 0.01). Loneliness did not differ across treatment arms. Discussion. Overall, these results extend prior findings relating loneliness to disability and decreased mobility to older individuals with type 2 diabetes and overweight or obesity. status each increase risk for loneliness [2, 3]. Roughly, 1. Introduction 25–43% of adults over the age of 70 report being lonely [4]. Loneliness is a subjective state, reflecting a lack of desired Loneliness is a well-established correlate of mental closeness with friends, family, and loved ones. Compared health, quality of life [5–7], and early mortality in older with structural measures of social contacts, counting an adults [8–14]. Moreover, loneliness has previously been individual’s opportunities for interaction with other people, shown to relate to disability [15, 16] and impaired mobility loneliness assesses the function of social interactions in [17]. For example, loneliness predicted a faster rate of ob- allowing a person to feel connected to others [1]. Living jectively-measured motor decline, defined by motor func- alone, widowhood, poor health status, and poor functional tion and muscle strength, over five years of follow-up among 2 Journal of Aging Research 985 men and women, with a mean age of 80 [17]. Peri- reassessed at year 15 to continue to follow diabetes and ssinotto and colleagues [13] found that loneliness was related aging-related outcomes, including measuring loneliness for to greater difficulty with activities of daily living and mobility the first time. %e study enrolled 5,145 men and women, at six year follow-up among over 14,000 men and women aged 45–76 at baseline. %e present study is cross-sectional over the age of 60 in the Health and Retirement Study. and derives variables from 15 year follow-up when partic- Higher levels of loneliness also predicted frailty as defined by ipants had a mean age of 75 (range: 61–92). All Look the Fried Formula at 4 year follow-up among 2,817 indi- AHEAD participants who were attending clinical visits were viduals over 60 years of age from the English Longitudinal included (n � 3187). Look AHEAD participants who were Study of Aging [15]. Interestingly, Hoogendijk and col- followed only through telephone interviews (n � 300) were leagues [18] reported that frailty increased the risk for excluded because loneliness was not queried. loneliness over 3 years, suggesting that the relationship between loneliness and physical function may be bidirec- 2.2. Study Interventions. Eligible patients were randomly tional [18]. assigned to participate in ILI (intervention group) or DSE Little is known about how loneliness relates to health (comparison group), with stratification according to clinical status among older individuals with type 2 diabetes. In the United States, 25% of individuals over the age of 65 have type site. Curricula for the two study groups were developed centrally and have been described in detail previously 2 diabetes [19] increasing the risk for early mortality, car- [27, 28]. diovascular disease, renal disease, dementia, functional impairment, depression, and vision impairment [20]. Al- though less stringent treatment goals can be recommended 2.3. Intensive Lifestyle Intervention (ILI). %e ILI included for elderly individuals, the need for diabetes self-manage- calorie restriction, low-fat diet, and increased physical activity ment remains including treatment adherence, nutrition, and and was designed to induce at least a 7% weight loss at year 1 exercise [21]. Social support improves diabetes self-man- and to maintain this weight loss in subsequent years. ILI agement, medication adherence, diet change, active lifestyles participants were assigned a calorie goal (1200–1800 kcal/d and, in some cases, glycemic control [22]. Conversely, based on initial weight), with less than 30% of total calories loneliness is associated with less physical activity [23, 24] and from fat (<10% from saturated fat) and a minimum of 15% of poorer sleep quality [25, 26]. As such, it is plausible that total calories from protein. %e exercise goal was at least loneliness may relate to health outcomes among elderly 175 minutes of physical activity per week, using activities individuals with type 2 diabetes but these associations have similar in intensity to brisk walking. ILI participants were seen not been established. for 3 groups and one individual session per month for the first Look AHEAD was a randomized controlled trial 6 months and 2 group, one individual session per month for designed to determine whether 10 years of intensive lifestyle the next 6 months, and at least monthly through year 10. ILI intervention (ILI), comprised of calorie restriction and was effective in inducing and sustaining weight losses relative physical activity promotion to achieve weight loss, improves to the control condition throughout follow-up [28]. health outcomes among older individuals with type 2 dia- betes and overweight or obesity, relative to a Diabetes Support and Education (DSE) control group. %e cohort was 2.4. Diabetes Support and Education (DSE). DSE featured reassessed for aging-related outcomes at 15-year follow-up, three group sessions per year focused on diet, exercise, and including loneliness measured for the first time. %e goal of social support during years 1 through 4. In subsequent years, this paper is to characterize the prevalence of loneliness the frequency was reduced to one session annually. among individuals with type 2 diabetes and overweight or obesity in the Look AHEAD cohort and to determine cross- sectional associations of loneliness score with self-reported 3. Measures disability and objective mobility and other health indicators, including HbA1c, quality of life, and depressive symptoms. 3.1. Loneliness. Loneliness was measured using the UCLA It is hypothesized that loneliness will relate to (1) greater Brief Loneliness Scale [29]. %e scale contains three ques- disability and decreased mobility and physical function, as tions: “How often do you feel that you lack companion- defined by the 400 m walk, grip strength, and the Short ship?”, “How often do you feel left out?”, and “How often do Physical Performance Battery and (2) higher HbA1c and you feel isolated from others?” Each item has the response depressive symptoms and lower quality of life. choices of “Hardly ever,” “Some of the time,” and “Often,” assigned scores 0, 1, and 2 respectively. %ese scores for each of the items are summed to give a total score. %e prevalence 2. Methods of loneliness has also been defined as reporting “Some of the 2.1. Research Design. Look AHEAD is a randomized, con- time” or “Often” relative to “Hardly ever” for at least one of trolled trial designed to test whether 10 years of ILI, com- the three questions: “How often do you feel that you lack bining calorie restriction and physical activity to produce companionship?”, “How often do you feel left out?” and weight loss, improves health outcomes among individuals “How often do you feel isolated from others?” [13]. %e with type 2 diabetes and overweight or obesity, relative to UCLA Brief Loneliness Scale was shown to have a strong DSE [27, 28] (see Supplementary File 2). %e cohort was correlation with the full UCLA Loneliness Scale (r � 0.82) Journal of Aging Research 3 scores of 0–3 based on increasing frequency and summing and to have reasonable internal consistency (Cronbach’s α � 0.72) [29]. the scores (range: 0–27). %e PHQ-9 has strong internal consistency (α � 0.89) and test-retest reliability (r � 0.84) in clinical samples [33]. %e PHQ-9 does not include a lone- 3.2. Disability and Physical Function liness item. 3.2.1. Pepper Assessment Tool for Disability (PAT-D). %e PAT-D is an 18-item self-report questionnaire designed to 3.3.2. Antidepressant Medications. Participants brought all assess disability in older adults. Participants are asked to rate: prescription medications to their annual clinic assessment “How much difficulty, if any, do you have with each of these visits, and these medications (but not the dosages) were activities? %ink about the past month. How hard was it to recorded by study staff. Antidepressant medications were do the activity because of your health?” Items include identified using the Food and Drug Administration classi- questions such as “Moving in and out of bed” and “Dressing fication system. yourself.” Responses range from “Usually did with no dif- ficulty” (1) to “Unable to do” (5) with the possibility of 3.3.3. Quality of Life. Quality of life was assessed using the endorsing “Usually did not do for other reasons.” Scores are SF-36 General Health questionnaire [34]. %e questionnaire averaged across the 18 items. %e PAT-D has shown strong asks participants: “In general, would you say your health internal consistency (α � 0.82) and test-retest reliability is. . .” with responses ranging from Excellent (1) to Poor (5) (r> 0.70). on a 1–5 scale. Lower values indicate better general health. 3.2.2. Physical Function Tests. Objective physical function 3.3.4.HbA1candDiabetesMedications. HbA1c was assayed was assessed in the full cohort at an average of 15–16 year from fasting blood samples. Six major classes of diabetes follow-up. %e Short Physical Performance Battery Ex- medications were categorized from the Food and Drug panded (SPPBexp) [30], a modestly expanded form of the Administration classification system and were used as Short Physical Performance Battery [31] designed to min- covariates in analyses of HbA1c. imize ceiling effects of the SPPB when used in well-func- tioning populations, was administered to assess lower extremity physical function. %e SPPB consists of standing 3.4. Statistical Analysis. Primary analyses were conducted balance tasks (side-by-side, semi- and full-tandem stands for using linear or logistic regression depending on the out- 10 seconds each), a 4 m walk to assess usual gait speed and come. Model 1 tested the association of loneliness, age, sex, time to complete five repeated chair stands. %e SPPBexp race, and ethnicity with the function- and health-related increased the holding time of the standing balance tasks to variables. Model 2 added depressive symptoms and anti- 30 seconds and added a single leg stand. %e SPPBexp depressant medications to determine whether loneliness component scores are calculated as the ratio of observed relates to the other variables independent of correlated performance to the best possible performance and summed constructs also known to relate to health outcomes. For the to provide a continuous score ranging from 0 to 3, with relationship of loneliness to HbA1c, the six major categories higher scores indicative of better performance. Usual of diabetes medications were added as covariates to Model 2. walking speed over 20 m and walking endurance over 400 m Treatment arm was added in Model 3 to determine whether were measured [32]. %e course was 20 m long and marked loneliness differs by ILI. by cones at each end. Participants were instructed to walk at PHQ-9 and PAT-D scales are extremely skewed, even their usual pace, and time to complete the first 20 m and the after log transformation, and thus were dichotomized at longer 400 m was recorded. Grip strength (kg) was measured their lowest value vs anything else. twice in each hand using an isometric Hydraulic Hand Dynamometer (Jamar, Bolingbrook, IL). %e maximum 4. Results force from two trials for the stronger hand was used in the 4.1. Descriptive Statistics. Descriptive statistics for baseline analyses. and the Look AHEAD E visit (15-year follow-up) are pre- sented in Table 1. %e balance afforded by the original 3.3. Other Health Indicators randomization was maintained at the 15-year visit: no differences in baseline age, sex, race, or Hispanic ethnicity 3.3.1. Personal Health Questionnaire-9 (PHQ-9). %e PHQ- were observed. However, several health indices continued to 9 is a self-administered questionnaire assessing depressed show intervention effects, including lower BMI (32.9 vs 33.6; mood and depression severity [33]. %e questionnaire asks p � 0.002), faster gait speed (4.85 vs 5.00 seconds; p � 0.01), “How often, over the past two weeks, have you been and less insulin use (43.4% vs 49.5%; p � 0.0009) in the ILI bothered by any of the following problems?” for nine compared with DSE groups. No differences in loneliness by questions, including “Little interest or pleasure in doing Look AHEAD treatment arm were observed (p � 0.11). things” and “Feeling down, depressed, or hopeless.” Re- sponse options include “Not at all,” “Several days,” “More than half of the days,” and “Nearly every day.” Depressed 4.2. Prevalence of Loneliness. %irty-eight percent of the mood severity was calculated by assigning response options Look AHEAD samples reported being lonely as defined by 4 Journal of Aging Research Table 1: Characteristics of participants with nonmissing loneliness scale at the Look AHEAD-E visit. Intervention arm Nonmissing Overall p value DSE ILI N 3190 1553 1634 Baseline characteristics Age 3190 58.3 (6.4) 58.3 (6.4) 58.2 (6.3) 0.7042 BMI 3190 35.9 (6.0) 36.0 (5.8) 35.7 (6.1) 0.1338 Gender Male 3190 1214 (38.1%) 581 (37.4%) 633 (38.7%) 0.4756 Female 1976 (61.9%) 973 (62.6%) 1003 (61.4%) Race/ethnicity White 1939 (60.8%) 950 (61.1%) 989 (60.5%) Black 3190 524 (16.4%) 260 (16.7%) 264 (16.2%) 0.6896 Hispanic 440 (13.8%) 203 (13.1%) 237 (14.5%) Others 287 (9.0%) 142 (9.1%) 145 (8.9%) LA-E visit Age 3190 72.7 (6.2) 72.7 (6.3) 72.7 (6.1) 0.7424 BMI 3019 33.2 (6.2) 33.6 (6.2) 32.9 (6.1) 0.0012 HbA1c% 2665 7.5 (1.5) 7.5 (1.5) 7.5 (1.4) 0.5779 PHQ-9 3052 2.7 (3.3) 2.8 (3.4) 2.6 (3.2) 0.1786 PHQ-9 � 0 3052 937 (30.7%) 458 (30.8%) 479 (30.6%) 0.9079 SF-36 general health 3156 2.9 (0.8) 2.9 (0.8) 2.9 (0.8) 0.4558 PAT-D 3157 1.5 (0.5) 1.5 (0.5) 1.5 (0.5) 0.5800 PAT-D � 1 3157 419 (13.3%) 212 (13.8%) 207 (12.8%) 0.4165 400 m walk time (min) 2632 6.7 (1.9) 6.8 (2.0) 6.7 (1.9) 0.6073 Gait speed test (sec) 2949 4.93 (1.67) 5.00 (1.71) 4.85 (1.62) 0.0168 Grip strength (right hand) 2702 23.9 (9.4) 23.8 (9.5) 24.0 (9.3) 0.5225 Taking antidepressants 2822 699 (24.8%) 337 (24.5%) 362 (25.0%) 0.7546 Taking any diabetes med 3067 2814 (91.8%) 1380 (92.3%) 1434 (91.2%) 0.2744 Biguanide 2967 2063 (69.5%) 1008 (69.5%) 1055 (69.6%) 0.9868 Insulin 2894 1344 (46.4%) 704 (49.5%) 640 (43.5%) 0.0010 Sulfonylurea 2863 979 (34.2%) 490 (35.1%) 489 (33.4%) 0.3460 TZD 2758 198 (7.2%) 94 (7.0%) 104 (7.4%) 0.6900 Loneliness 3190 3.86 (1.38) 3.90 (1.42) 3.82 (1.34) 0.1164 Values are given as mean (SD) or N (%) endorsing “Sometimes” to at least on the three questions on Loneliness did not correlate with the 400-meter walk test the UCLA Brief Loneliness Survey. Nine percent reported speed (β � 0.03± 0.03; p � 0.2375). “Often” for at least one question. After further adjustment for depression symptoms and antidepressant medication use (Table 2, Model 2), greater loneliness continued to significantly relate to higher Pepper 4.3. Differences in Loneliness Scores by Demographics and Disability Test scores (OR � 1.24; p � 0.0018) and slower gait BMI. As seen in Supplementary Table 1, levels of loneliness (β � 0.10± 0.03; p � 0.0003), but the association with grip differed meaningfully by demographics and BMI. %e mean strength was reduced to nonsignificance (β � −0.17± 0.12; loneliness score was higher in women compared to men p � 0.1592). Again, these associations were not substantially (p< 0.0001), individuals of Black, Hispanic, or other races and altered by statistical control for treatment arm (Table 2, ethnicities compared to whites (p � 0.0001), individuals with Model 3). less formal education (p< 0.0001), and individuals who have a 2 2 BMI≥ 40 kg/m at baseline (p � 0.02). A BMI≥ 40 kg/m at 15 year follow-up also was strongly related to loneliness 4.5. Loneliness, Depressive Symptoms, Antidepressant Medi- (p< 0.0001), but no differences in loneliness by age were cations,andQualityofLife. In models adjusting for age, sex, observed at 15 year follow-up (p � 0.38). race, and ethnicity (Table 2, Model 1), greater loneliness was significantly related to higher PHQ-9 scores (OR � 1.89; p< 0.0001) and a greater likelihood of taking antidepressant 4.4.Loneliness,Disability,andMobility. In models adjusting medications (OR � 1.32; p< 0.0001). After further adjust- for age, sex, race, and ethnicity (Table 2, Model 1), greater ment for antidepressant medication use (Table 2, Model 2), loneliness was significantly related to greater self-report of greater loneliness continued to relate to higher PHQ-9 disability on the Pepper Disability Test (OR � 1.47; scores (OR � 1.75; p< 0.0001). Similarly, after controlling p< 0.0001), slower gait speed (β � 0.19± 0.02; p< 0.0001), for PHQ-9 scores, greater loneliness continued to relate to and weaker hand grip (β � −0.39± 0.10; p< 0.0001). antidepressant use (OR � 1.12; p< 0.0001). %ese Journal of Aging Research 5 Table 2: Adjusted associations with loneliness. Model 1 Model 2 Model 3 Outcome Beta SE p value Beta SE p value Beta SE p value Gait speed test (seconds) 0.192 0.022 <0.0001 0.097 0.026 0.0002 0.096 0.026 0.0003 Grip strength (right hand) −0.382 0.097 <0.0001 −0.170 0.117 0.1471 −0.168 0.118 0.1530 400 m walk time 0.034 0.029 0.2451 0.038 0.035 0.2759 0.037 0.035 0.2839 SF-36 general health 0.140 0.011 <0.0001 0.035 0.012 0.0057 0.035 0.013 0.0058 HbA1c% 0.030 0.020 0.1372 0.009 0.023 0.6868 0.010 0.023 0.6632 OR 95% CI p value OR 95% CI p value OR 95% CI p value PAT-D> 1 1.470 1.313–1.645 <0.0001 1.243 1.085–1.424 0.0017 1.245 1.087–0.427 0.0016 PHQ-9> 0 1.897 1.723–2.088 <0.0001 1.752 1.585–1.938 <0.0001 1.754 1.586–1.939 <0.0001 Taking antidepressants 1.319 1.242–1.401 <0.0001 1.126 1.048–1.211 0.0013 1.127 1.048–1.211 0.0012 Note. Model 1: adjusts for age, sex, and race/ethnicity. Model 2: Model 1 plus depressive symptoms (PHQ-9) and antidepressant medication use. Also includes major diabetes med categories for HbA1c outcome (biguanide, insulin, sulfonylurea, and TZD) PHQ-9 outcome does not adjust for depressive symptoms. Taking antidepressants outcome does not adjust for antidepressant medication use. Model 3: Model 2 plus treatment arm. associations were not substantially altered by statistical quality of life after similar adjustment. %ese results identify control for treatment arm (Table 2, Model 3). loneliness as an important correlate of physical and mental In models adjusting for age, sex, race, and ethnicity health among aging individuals with an elevated body mass (Table 2, Model 1), greater loneliness was significantly re- index and type 2 diabetes. lated to lower self-rated general health on the SF-36 After adjustment for demographic variables, loneliness (β � 0.14± 0.01; p< 0.0001), and this association remained also correlated with a weaker hand grip but the association significant after controlling for depressive symptoms and weakened to nonsignificance after further adjustment for antidepressant medication use (β � 0.03± 0.01; p � 0.0063) depressive symptoms and use of antidepressant medications, (Table 2, Model 2). indicating that loneliness is not independently related to hand grip strength in this study. Loneliness did not sig- nificantly relate to HbA1c or the 400-meter walk test in any 4.6.LonelinessandHbA1c. Loneliness did not correlate with of the models. HbA1c in models adjusted for age, sex, race, and ethnicity %e prevalence of loneliness was similar to prior research (β � 0.03± 0.02; p � 0.1297), nor with further adjustment for in elderly individuals. Roughly 38% of these individuals with depressive symptoms, antidepressant medications, glucose- type 2 diabetes and obesity or overweight reported loneliness lowering medication, or treatment arm. at least some of the time, and 9% endorsed experiencing at least one of the loneliness questions often. In the most direct comparison, Perissinotto and colleagues used the UCLA 4.7. Interaction with Treatment Arm. Treatment arm inter- Brief Loneliness Scale (as was used in this paper) to estimate acted with loneliness in its association with two mobility prevalence of loneliness in the Health and Retirement Study, measures: 400-meter walk test (p � 0.03) and gait speed including noninstitutionalized individuals over the age of 65 (p � 0.03; Table 3). In each case, physical function was [13]. Forty-three percent endorsed loneliness on one of the similar across the spectrum of loneliness scores in the ILI, questions at least some of the time, and 13% reported feeling whereas higher loneliness was related to poorer physical lonely often, suggesting that the prevalence of loneliness in function in DSE. Supplementary Figures 1(a) and 1(b) il- th Look AHEAD is roughly comparable with the U.S. pop- lustrate the interactions with loneliness depicted at the 10 th ulation over the age of 65. (loneliness � 3) and 90 (loneliness � 6) percentiles of Levels of loneliness did not differ by randomized loneliness score. treatment arm. %is is likely due to the measurement of %ere was also an interaction of loneliness and treatment loneliness 15 years after the initiation of the intervention, arm in their associations with HbA1c (p � 0.04, Table 3). In and 5 years following the end of the intervention. More those with lower loneliness scores, there was no differential research is needed to determine the impact of lifestyle in- effect between treatment arms. However, in those with tervention for weight loss on loneliness, particularly in in- higher loneliness scores, HbA1c was lower in the ILI dividuals with BMI≥ 40, who showed an increased compared to the DSE (Supplementary Figure 1(c)). loneliness scores both at baseline and 15 year follow-up. Loneliness also appeared to moderate the impact of ILI 5. Discussion and DSE on mobility. %e interaction indicated that the In this sample of older individuals who have type 2 diabetes long-term effect of ILI on gait speed and the 400 m walk test and overweight or obesity, loneliness was associated with did not differ by loneliness. However, in DSE, loneliness higher disability scores and slower gait speed after statistical related to poorer outcomes for gait speed and the 400 m walk adjustment for several potential confounders. Loneliness test, leading to treatment arm by loneliness interactions. %is was also associated with higher depressive symptoms and suggests that ILI benefited mobility regardless of loneliness antidepressant medication use and poorer health-related level, whereas DSE predicted a lesser overall benefit and the 6 Journal of Aging Research Table 3: Exploring interactions with loneliness. It is important to note that the present study did not measure social isolation, a related but distinct measure of the Loneliness by treatment arm Outcome structure of social contacts. Social isolation also predicts (p value) aging-related outcomes [9, 12]. Indeed, several research Gait speed test (seconds) 0.0325 studies have compared the impact of loneliness to social Grip strength (right hand) 0.0568 isolation to determine whether the perception or structure of 400 m walk time 0.0253 social contacts has a greater impact on health, but research HbA1c% 0.0441 remains mixed [1, 6, 9, 15, 16, 23, 35]. It is also plausible that SF-36 general health 0.2164 loneliness and social isolation have synergistic effects PAT-D> 1 0.1308 wherein those with both conditions are at the greatest health PHQ-9> 0 0.2819 risk [36]. Future research in Look AHEAD should incor- Taking antidepressants 0.8536 porate a measure of social isolation, in addition to loneliness, to determine the relative contributions of each and the potential for compounding risks. benefit varied by loneliness. As DSE had minimal inter- Given the health risks, it is encouraging that interven- tions are being tested to reduce loneliness in the elderly. For vention, it is plausible that the relationship of loneliness to mobility in DSE is reflective of prior reports of associations example, Silver Sneakers, a gym membership and exercise with health outcome in more general populations, e.g., classes, was shown to increase physical activity and to reduce [15–17]. However, the impact of ILI on mobility may have social isolation and loneliness compared to matched controls blunted relationships with loneliness. [37]. In addition, a pilot, m-Health intervention targeting It further appeared that ILI was more effective in maladaptive cognitions in elderly individuals who are ex- reducing HbA1c compared with DSE among individuals periencing loneliness reduced these symptoms over three months [38]. with higher loneliness, whereas there was little difference by treatment arm among those with lower loneliness Although this study had several strengths, including an aging sample with type 2 diabetes, a large sample size, and levels. It is plausible that ILI may have been more effective among individuals with higher loneliness scores than objective measures of physical function, it is important to DSE due to the differential contacts with providers and note limitations. First, as this study was cross-sectional, the other participants in ILI. However, it should be recog- direction of association cannot be determined. Indeed, nized that the interaction analyses were exploratory and prior research suggests that the associations of loneliness not hypothesis driven. with depression and disability may be bidirectional [7, 18]. Taken together, these findings from a sample of older Future, longitudinal research will be needed to resolve participants who have type 2 diabetes and overweight or directionality in this cohort. In addition, the loneliness obesity share many similarities to the prior literature in- questionnaire was only included in the clinic questionnaire, which excluded 9.4% of participants who completed tele- volving older people without diabetes. Specifically, we find loneliness to relate to disability scores, objective gait speed, phone interviews but may have had more difficulty at- tending visits in the clinic. Neither social isolation nor depressive symptoms and use of antidepressant medications, and health-related quality of life, consistent with prior re- contemporaneous socioeconomic status was measured in ports [5, 7, 13, 15–18]. In contrast, we did not support prior Look AHEAD and may serve as confounders of the rela- studies finding relationships of loneliness with glycemic tionship between loneliness and the health outcomes. control. Given that diabetes impacts one in four elderly Lastly, although we did not see evidence for differential loss adults in the United States, requires a complicated self- of follow-up between treatment groups, we cannot rule out management regimen, and portends an increased burden that this may have introduced bias in differences and associations. from multiple diseases, it is critical to identify factors that may further compound disease risk. Overall, this study demonstrates that loneliness relates to greater disability, slower gait speed, depressive symptoms, One challenge of the literature relating loneliness to health outcomes is the variety of different scales used. Meta- antidepressant medication use, and poorer quality of life among older individuals who have type 2 diabetes and are analysis and reviews, e.g., [1, 4], identify numerous scales designed to characterize loneliness, with some scales overweight or obese. Future longitudinal research needs to showing overlap with structural measures of social con- address questions such as the potential for bidirectional nection. Some of the prior research has even relied on a relationships with loneliness and the longer-term impacts on single question to index loneliness. We used the UCLA Brief health outcomes. Loneliness Scale (three items). %is scale shows a strong correspondence with the original, 20-item questionnaire Data Availability [29] and has previously been demonstrated to relate to behavioral and physical outcomes, including depression [7], All Look AHEAD data will be made available through the physical function [16], and mortality [9], among other National Institute of Diabetes, Digestive, and Kidney Disease outcomes. %us, the scale was a reasonable choice to rep- data repository within two years in accordance with the resent the health impacts of loneliness. policy of the Look AHEAD clinical trial. Journal of Aging Research 7 between loneliness score and treatment arm in relation to Disclosure th 400 meter walk time. Interaction illustrated using the 10 th %e opinions expressed in this paper are those of the authors (loneliness � 3) and 90 (loneliness � 6) percentiles for the and do not necessarily reflect the views of the NIH or other loneliness score. Supplementary Figure 1(b): interaction funding sources. between loneliness score and treatment arm in relation to gait speed. Interaction illustrated using the th th 10 (loneliness � 3) and 90 (loneliness � 6) percentiles for Conflicts of Interest the loneliness score. Supplementary Figure 1(c): interaction All authors report no conflicts of interest. between loneliness score and treatment arm in relation to th hemoglobin A1c. Interaction illustrated using the 10 th (loneliness � 3) and 90 (loneliness � 6) percentiles for the Acknowledgments loneliness score. (Supplementary Materials) %is study was funded by the National Institutes of Health through cooperative agreements with the National Institute of References Diabetes and Digestive and Kidney Diseases (DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, [1] N. Leigh-Hunt, D. Bagguley, K. 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Published: Oct 30, 2020

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