Kim, Kim, and Lee: Associations of Insulin Resistance, Type 2 Diabetes, and Physical Activity with Knee Osteoarthritis in Older Women
Abstract
PURPOSE
This study aimed to analyze the associations among insulin resistance (IR), type 2 diabetes mellitus (T2DM), physical activity, and knee osteoarthritis (KOA) in older women.
METHODS
A total of 2,217 women aged ≥65 years who participated in the Korea National Health and Nutrition Examination Survey (2009–2013) were included. IR was assessed using the triglyceride-glucose body mass index, and participants were classified as normal or abnormal based on cutoffs. T2DM was defined as having a fasting glucose level >126 mg/dL, a physician-diagnosed diabetes history, or current treatment for diabetes. Physical activity was assessed using the International Physical Activity Questionnaire and categorized by whether participants engaged in ≥150 min/week of light-intensity physical activity (LPA) or moderate-to-vigorous physical activity (MVPA). KOA was defined as Kellgren-Lawrence (KL) grade ≥2, and categorized as follows: KL 0–1=normal, KL 2=light KOA, KL 3–4=moderate-to-severe KOA.
RESULTS
Logistic regression showed significantly higher KOA risk in the abnormal IR group (OR=1.768, 95% CI=1.486–2.105) and T2DM group (OR=1.311, 95% CI=1.054–1.631) compared to the normal group. Participants with <150 min/week of LPA had higher KOA risk (OR=1.378, 95% CI=1.158–1.639) than those with ≥150 min/week. In the IR and T2DM groups, participants engaging in <150 min/week of LPA had significantly higher odds of moderate-to-severe KOA compared to those with ≥150 min/week.
CONCLUSIONS
Engaging in >150 min/week of LPA may be a practical and effective strategy for the prevention of KOA in older women with impaired glucose metabolism.
Keywords: Insulin resistance, Type 2 diabetes melitus, Light intensity physical activity, Knee osteoarthritis
INTRODUCTION
The knee joint is the largest synovial joint in the human body and is subject to substantial mechanical stress due to its frequent use; consequently, it is known to be the most commonly affected site of osteoarthritis [ 1]. Indeed, recent studies have reported that knee osteoarthritis (KOA) accounts for more than 80% of the total disease burden attributable to osteoarthritis, and it is estimated that more than one-fifth of adults aged 40 years and older worldwide are affected [ 2]. In addition, the prevalence of KOA tends to increase with age, and a particularly high prevalence has been reported among older women, largely due to postmenopausal reductions in estrogen levels [ 3]. In Korea, the prevalence of KOA among older women has been reported to be as high as 50.2%, and with ongoing population aging, this prevalence is expected to increase further, underscoring the need for effective preventive strategies [ 4].
Historically, KOA was predominantly regarded as a condition arising from structural joint damage caused by mechanical stress. However, ac-cumulating evidence has demonstrated that systemic metabolic abnormalities and chronic inflammatory states are closely associated with the development of KOA. Consequently, there has been a growing shift to-ward conceptualizing KOA not merely as a localized joint disorder but as a metabolic and inflammatory disease [ 5, 6]. In this context, recent studies have shown that insulin plays a critical role in maintaining the structural integrity and functional capacity of articular cartilage by promoting the synthesis of type II collagen and proteoglycans in chondrocytes, thereby preventing cartilage degradation. Conversely, chronic hyperglycemia has been shown to induce oxidative stress and promote the accumulation of advanced glycation end products (AGEs), which can impair chondrocyte function and ultimately lead to cartilage stiffening and structural deterioration of the joint. These findings have brought insulin resistance (IR) and type 2 diabetes mellitus (T2DM) to the fore-front as emerging risk factors for the development of KOA [ 7, 8]. Indeed, a growing body of clinical and epidemiological evidence, both domestically and internationally, has established abnormal insulin resistance and T2DM as independent risk factors for KOA. Furthermore, given the rising prevalence of obesity and ongoing population aging, demographic shifts are expected to expand the population vulnerable to increased insulin resistance and T2DM. This trend further underscores the importance of developing KOA prevention strategies that explicitly account for impaired glucose metabolism [ 9– 11].
Meanwhile, regular participation in moderate-to-vigorous physical activity has been widely recognized to provide a range of health benefits, including improvements in cardiovascular health and metabolic function, as well as the maintenance of the musculoskeletal system, regardless of sex or age [ 12, 13]. However, among older adults, engagement in regular moderate-to-vigorous physical activity may be limited due to factors such as fear of falls associated with declines in physical function, reduced recovery capacity, and limited access to exercise-related information and facilities [ 14]. In contrast, light-intensity physical activity, including walking, has gained attention as a feasible alternative that older adults can continuously practice to obtain health benefits, given its ease of implementation and favorable safety profile, and recent evidence suggests that it may also play a positive role in the prevention of type 2 diabetes mellitus and knee osteoarthritis [ 15– 18]. With regard to type 2 diabetes mellitus, Amagasa et al. [ 15] reported that light-intensity physical activity plays a positive role in improving glucose metabolism independently of moderate-to-vigorous physical activity, while Dempsey et al. [ 16] demonstrated that replacing sedentary time with light-intensity physical activity may serve as an effective strategy for the prevention of type 2 diabetes mellitus. In addition, with respect to knee osteoarthritis, Li et al. [ 17], in a prospective cohort study based on UK Biobank data, demonstrated that greater time spent in light-intensity physical activity after midlife was associated with a reduced risk of developing knee osteoarthritis, while Lo et al. [ 18], in a cohort study of middle-aged and older adults in the United States, reported that individuals who participated in walking activities exhibited reduced progression of knee pain and medial knee joint space narrowing compared with those who did not engage in walking activities. Taken together, these previous studies suggest that regular light-intensity physical activity in older age may be considered a protective factor closely associated with both type 2 diabetes mellitus and knee osteoarthritis, and, in particular, that it may play a positive role in the prevention of knee osteoarthritis, in contrast to type 2 diabetes mellitus, thereby potentially mitigating the risk of knee osteoarthritis associated with insulin resistance and type 2 diabetes mellitus. Furthermore, light-intensity physical activity is expected to serve as an effective preventive strategy for knee osteoarthritis among older adults who experience substantial limitations in physical activity and safety concerns due to conditions such as obesity, sarcopenia, and frailty. However, to date, the majority of previous studies involving older adults have been limited to fragmentary analyses examining either the association between insulin resistance and type 2 diabetes mellitus and knee osteoarthritis or the association between light-intensity physical activity and knee osteoarthritis. Therefore, the present study aimed to analyze the association between knee osteoarthritis and combined levels of light-intensity physical activity in conjunction with insulin resistance and type 2 diabetes mellitus, which are key risk factors for knee osteoarthritis and represent vulnerable metabolic conditions in older age, and to provide foundational evidence for the development of preventive strategies for knee osteoarthritis in older adults.
METHODS
1. Data collection and study population
This study utilized data from the 2009–2013 Korea National Health and Nutrition Examination Survey (KNHANES), which included anthropometric and blood biomarkers required for the calculation of surrogate indicators of insulin resistance, information on physical activity, and Kellgren–Lawrence (KL) grading for the radiographic diagnosis of knee osteoarthritis. The initial study population consisted of 3,719 women aged 65 years and older. Subsequently, a total of 1,502 participants were excluded, including 165 individuals with missing body composition and anthropometric measurements, 479 individuals with missing fasting glucose or blood lipid data, 18 individuals who were taking glucose-lowering or lipid-lowering medications on the day of measurement, 507 individuals with missing KL grades from knee radiographs, 59 individuals with missing physical activity data, 32 individuals with missing socioeconomic variables, and 242 individuals with missing health-related variables. As a result, a final sample of 2,217 participants was included in the data analysis for this study. This study was conducted with approval from the Institutional Review Board of C University (Approval No. 7001066-202412-HR-082). Body composition and anthropometric measurements were obtained while participants were wearing examination gowns. Height and body weight were measured to the nearest centimeter and kilogram using a stadiometer (Seca 225, Seca, Hamburg, Germany) and a digital scale (GL-6000-20, Gtech, Uijeongbu, Korea), respectively.
2. Assessment of body composition and anthropometric measurements
Body composition and anthropometric measurements were obtained while participants were wearing examination gowns. Height and body weight were measured to the nearest centimeter and kilogram using a stadiometer (Seca 225, Seca, Hamburg, Germany) and a digital scale (GL-6000-20, Gtech, Uijeongbu, Korea), respectively. Body mass index (BMI) was subsequently calculated using the formula body weight (kg) divided by height squared (m2). Waist circumference was measured twice in centimeters at the midpoint between the lower margin of the rib cage and the iliac crest using a non-elastic measuring tape for anthropometric assessment (Seca 200, Seca, Hamburg, Korea), and the mean value was used for analysis.
3. Radiographic assessment of knee osteoarthritis
Radiographic images of both knee joints were obtained using Digi-RAD-PG (SITEC, Seongnam, Korea) while participants stood in a weight-bearing position with the knees flexed at approximately 30°, and images were acquired in the anteroposterior and lateral views. The radiographs were independently evaluated by two board-certified radiologists using the KL grading system, which ranges from grade 0 to grade 4, and concordant grades were assigned as the final grade. When there was a one-grade discrepancy between the two radiologists, the higher grade was accepted as the final grade, whereas when the discrepancy exceeded one grade, the grade that matched the evaluation of a third radiologist was assigned as the final grade. Based on the assigned grades, knee osteoarthritis was defined as a KL grade of 2 or higher [ 19]. Furthermore, according to the degree of joint degeneration by KL grade, participants were categorized as normal (KL grades 0–1), mild knee osteoarthritis (KL grade 2), or moderate-to-severe knee osteoarthritis (KL grades 3–4) [ 19].
4. Blood analysis and calculation of insulin resistance indices
Blood samples were collected from the antecubital vein of the non-dominant arm after a minimum fasting period of 8 hours. The collected blood samples were stored in NaF tubes and SST tubes for fasting blood glucose testing and blood lipid analysis, respectively, and blood samples in NaF tubes were mixed for 10 minutes using a roller mixer to ensure adequate mixing of anticoagulant and blood, while blood samples in SST tubes were allowed to stand at room temperature for 30 minutes and were then centrifuged at 3,000 rpm for 15 minutes. The specimens were subsequently collected by an external laboratory for analysis, and fasting blood glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides were analyzed using enzymatic methods.
Based on the analyzed blood biomarkers, the triglyceride–glucose body mass index (TyG-BMI), which has been reported as a surrogate marker that best reflects insulin resistance in the Korean population, was calculated, and participants were classified as “ Normal” or “Abnormal” using a cutoff value of 111.5, which has been reported as a discriminative threshold reflecting increased insulin resistance in women in studies evaluating insulin resistance risk based on blood lipid profiles [ 20, 21]. The formula used to calculate TyG-BMI in this study was as follows [ 22].
TyG-BMI=Ln[triglcyeride (mg/dL)×fasting blood glucose (mg/dL)/2]×body mass index
5. Definition of type 2 diabetes mellitus
Type 2 diabetes mellitus was defined based on fasting blood glucose levels according to the diagnostic criteria of the American Diabetes Association as having a fasting blood glucose level of ≥126 mg/dL, having received a physician diagnosis of diabetes, or currently undergoing treatment for diabetes [ 23].
6. Classification according to light-intensity and moderate- to-vigorous physical activity
Physical activity time by intensity was calculated based on responses to the International Physical Activity Questionnaire, which assesses the number of days and duration of participation in physical activity by intensity per week [ 24]. Light-intensity physical activity was calculated by multiplying the number of days participants engaged in walking activities during the week by the daily duration of participation, and based on the calculated weekly walking time, participants were classified as “≥150 min/week” or “<150 min/week” according to the walking practice rate criteria of the Korea National Health and Nutrition Examination Survey [ 25]. Similarly, moderate-to-vigorous physical activity was calculated by multiplying the number of days participants engaged in moderate- and vigorous-intensity physical activity by the daily duration of participation, after which the weekly time spent in vigorous-intensity physical activity was multiplied by two and added to the weekly time spent in moderate-intensity physical activity to derive the total moderate-to-vigorous physical activity time. Participants were then classified as “≥150 min/week” or “<150 min/week” based on the World Health Organization physical activity guidelines recommending at least 150 minutes of physical activity per week for health benefits [ 26].
7. Classification of other covariates
Covariates included socioeconomic factors such as monthly household income, educational level, marital status, and residential area, as well as health-related factors including smoking, binge drinking, moderate-to-vigorous physical activity, muscle-strengthening exercise, energy intake, menopause age, hypertension, dyslipidemia, and diabetes. Monthly household income was assessed as the average monthly income of household members in units of 10,000 KRW, educational level was categorized as “ lower than elementary school,” “ middle or high school,” or “ over than college,” marital status was categorized as “ married” or “ unmarried/divorced/widowed,” and residential area was categorized as “ urban” or “ rural.” Smoking was defined as having a lifetime smoking history of five packs or more or being a current smoker [ 27], and binge drinking was defined as consuming five or more alcoholic drinks on a single occasion [ 28]. Energy intake was assessed as daily food intake measured in grams, and hypertension was defined based on physician diagnosis.
8. Data analysis
In this study, continuous variables were presented as means and standard deviations (SD), and categorical variables were presented as frequencies and percentages (%). First, independent-samples t-tests were performed to compare continuous variables according to the presence of knee osteoarthritis, insulin resistance status, type 2 diabetes mellitus status, and physical activity levels, and chi-square tests were conducted to compare categorical variables. Subsequently, binary logistic regression analyses were performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for knee osteoarthritis according to independent levels of insulin resistance, type 2 diabetes mellitus status, and physical activity. In addition, odds ratios and 95% confidence intervals for knee osteoarthritis were calculated according to light-intensity physical activity levels within the insulin resistance and type 2 diabetes mellitus groups.
All statistical analyses were performed using SPSS-PC version 28.0 (IBM Corp., Armonk, NY, USA), and the level of statistical significance for hypothesis testing was set at α=0.05.
RESULTS
1. Comparison of variables according to presence of knee osteoarthritis
Table 1 presents the comparison of variables according to the presence of knee osteoarthritis (KL grades 0–1 vs. KL grade ≥2). The results showed that age ( p <.001), body weight ( p <.001), body mass index ( p <.001), waist circumference ( p <.001), hypertension ( p <.001), type 2 diabetes mellitus ( p =.015), fasting blood glucose ( p =.002), triglycerides ( p =.008), and TyG-BMI ( p <.001) were significantly higher in the KOA group than in the non-KOA group, whereas height ( p =.011), educational level ( p <.001), proportion of married individuals ( p <.001), proportion of urban residence ( p =.004), light-intensity physical activity time ( p =.009), and menopause age ( p =.001) were significantly lower in the KOA group.
Table 1.
Descriptive statistics of measured parameters according to presence of knee osteoarthritis
|
Variables |
Total (n=2,217/100.0%) |
Non-KOA (n=820/37.0%) |
KOA (n=1,397/63.0%) |
p-value |
|
KL grade |
2.10±1.40 |
0.49±0.50 |
3.05±0.74 |
<.001 |
|
Age (year) |
71.9±4.6 |
70.7±4.4 |
72.6±4.6 |
<.001 |
|
Body weight (kg) |
55.6±8.7 |
54.2±8.5 |
56.6±8.9 |
<.001 |
|
Height (cm) |
151.2±5.7 |
151.6±5.8 |
151.0±5.6 |
.011 |
|
BMI (kg/m2) |
24.3±3.2 |
23.6±3.1 |
24.8±3.3 |
<.001 |
|
WC (cm) |
83.1±9.1 |
81.5±9.1 |
84.2±9.3 |
<.001 |
|
Socio-economic status |
|
|
|
|
|
Household income (10,000 won/month) |
176.8±228.2 |
183.3±231.1 |
172.3±225.7 |
.268 |
|
Education, n (%) |
|
|
|
<.001 |
|
Lower than elementary school |
1,809 (81.6) |
633 (77.2) |
1,176 (84.2) |
|
|
Middle/high school |
368 (16.6) |
167 (20.4) |
201 (14.4) |
|
|
Over than college |
40 (1.8) |
20 (2.4) |
20 (1.4) |
|
|
Marital status, n (%) |
|
|
|
<.001 |
|
Married |
1,130 (51.0) |
468 (57.1) |
662 (47.4) |
|
|
Unmarried/widowed/divorced |
1,087 (49.0) |
352 (42.9) |
735 (52.6) |
|
|
Region, n (%) |
|
|
|
.004 |
|
Urban |
1,469 (66.3) |
574 (70.0) |
895 (64.1) |
|
|
Rural |
748 (33.7) |
246 (30.0) |
502 (35.9) |
|
|
Health related parameters |
|
|
|
|
|
Smoking, n (%) |
164 (7.4) |
62 (7.6) |
102 (7.3) |
.822 |
|
Binge drinking, n (%) |
34 (1.5) |
13 (1.6) |
21 (1.5) |
.879 |
|
LPA (min/week) |
187.5±232.3 |
204.7±240.2 |
177.7±227.0 |
.009 |
|
MVPA (min/week) |
132.5±313.7 |
137.5±331.7 |
129.6±302.8 |
.569 |
|
Energy intake (g/day) |
1,484.0±540.1 |
1,508.5±546.8 |
1,469.6±535.8 |
.104 |
|
Menopause age (year) |
48.6±5.5 |
49.1±5.4 |
48.3±5.5 |
.001 |
|
Hypertension, n (%) |
734 (33.1) |
254 (31.0) |
480 (34.4) |
.100 |
|
Type 2 Diabetes Mellitus, n (%) |
518 (23.4) |
168 (20.5) |
350 (25.1) |
.014 |
|
Laboratory parameters |
|
|
|
|
|
FBG (mg/dL) |
102.6±23.0 |
100.6±20.7 |
103.8±24.2 |
.002 |
|
TG (mg/dL) |
143.3±89.9 |
137.2±71.2 |
146.8±99.1 |
.008 |
|
TC (mg/dL) |
198.2±38.3 |
197.8±36.9 |
198.5±39.2 |
.657 |
|
LDL-C (mg/dL) |
121.9±34.2 |
122.1±33.2 |
121.7±34.8 |
.801 |
|
HDL-C (mg/dL) |
47.7±11.0 |
48.2±11.0 |
47.4±11.0 |
.100 |
|
TyG-BMI |
114.8±17.6 |
110.7±16.5 |
117.1±17.8 |
<.001 |
2. Comparison of variables according to insulin resistance status and type 2 diabetes mellitus
Table 2 presents the comparison of variables according to insulin resistance status and the presence of type 2 diabetes mellitus. First, with respect to insulin resistance status, the Abnormal group showed significantly higher fasting blood glucose ( p <.001), body weight ( p <.001), height ( p <.001), body mass index ( p <.001), waist circumference ( p <.001), proportion of urban residence ( p <.001), binge drinking ( p =.010), energy intake ( p =.046), KL grade ( p <.001), knee osteoarthritis prevalence ( p <.001), and triglyceride ( p <.001) compared with the Normal group, whereas age ( p <.001), light-intensity physical activity time ( p =.011), and high-density lipoprotein cholesterol ( p <.001) were significantly lower.
Table 2.
Descriptive statistics of measured parameters according to insulin resistance status and presence of type 2 diabetes mellitus
|
Variables |
Insulin resistance status |
p-value |
Type 2 Diabetes Mellitus |
p-value |
|
Normal (n=1,006/45.4%) |
Abnormal (n=1,211/54.6%) |
Non-T2DM (n=1,699/76.6%) |
T2DM (n=518/23.4%) |
|
TyG-BMI |
99.7±8.9 |
127.3±12.4 |
<.001 |
112.3±16.4 |
122.8±18.9 |
<.001 |
|
FBG (mg/dL) |
97.4±20.8 |
106.9±23.8 |
<.001 |
94.9±9.2 |
127.8±34.0 |
<.001 |
|
Age (year) |
72.3±4.7 |
71.5±4.5 |
<.001 |
71.8±4.6 |
71.9±4.6 |
.824 |
|
Body weight (kg) |
49.5±5.9 |
60.7±7.1 |
<.001 |
54.8±8.4 |
58.2±9.1 |
<.001 |
|
Height (cm) |
150.8±5.9 |
151.6±5.4 |
<.001 |
151.0±5.7 |
151.9±5.6 |
.002 |
|
BMI (kg/m2) |
21.7±1.9 |
26.4±2.4 |
<.001 |
24.0±3.0 |
25.2±3.5 |
<.001 |
|
WC (cm) |
76.7±6.9 |
88.4±7.1 |
<.001 |
82.1±8.9 |
86.5±9.2 |
<.001 |
|
Socio-economic status |
|
|
|
|
|
|
|
Household income (10,000 won/month) |
178.9±238.6 |
175.0±219.2 |
.694 |
180.1±231.9 |
165.9±215.4 |
.214 |
|
Education, n (%) |
|
|
.914 |
|
|
.411 |
|
Lower than elementary school |
823 (81.8) |
966 (81.4) |
|
1,377 (81.0) |
432 (83.4) |
|
|
Middle/high school |
164 (16.3) |
204 (16.8) |
|
289 (17.0) |
79 (15.3) |
|
|
Over than college |
19 (1.9) |
21 (1.8) |
|
33 (2.0) |
7 (1.3) |
|
|
Marital status, n (%) |
|
|
.949 |
|
|
.108 |
|
Married |
512 (50.9) |
618 (51.0) |
|
882 (51.9) |
248 (47.9) |
|
|
Unmarried/widowed/divorced |
494 (49.1) |
593 (49.0) |
|
817 (48.1) |
270 (52.1) |
|
|
Region, n (%) |
|
|
<.001 |
|
|
.027 |
|
Urban |
626 (62.2) |
843 (69.6) |
|
1,105 (65.0) |
364 (70.3) |
|
|
Rural |
380 (37.8) |
368 (30.4) |
|
594 (35.0) |
154 (29.7) |
|
|
Health related parameters |
|
|
|
|
|
|
|
Smoking, n (%) |
80 (8.0) |
84 (6.9) |
.363 |
112 (6.6) |
52 (10.0) |
.009 |
|
Binge drinking, n (%) |
8 (0.8) |
26 (2.1) |
.010 |
28 (1.6) |
6 (1.2) |
.427 |
|
LPA (min/week) |
201.3±249.1 |
176.1±216.7 |
.011 |
187.5±232.0 |
187.7±233.5 |
.987 |
|
MVPA (min/week) |
137.0±325.9 |
128.8±303.4 |
.541 |
131.6±308.7 |
135.5±330.2 |
.806 |
|
Energy intake (g/day) |
1,458.9±551.2 |
1,504.9±530.0 |
.046 |
1,492.6±542.0 |
1,455.8±533.4 |
.175 |
|
Menopause age (year) |
48.5±5.5 |
48.7±5.5 |
.307 |
48.7±5.5 |
48.3±5.5 |
.139 |
|
Hypertension, n (%) |
317 (31.5) |
417 (34.5) |
.142 |
557 (32.8) |
178 (34.4) |
.504 |
|
KL grade |
1.89±1.40 |
2.28±1.38 |
<.001 |
2.07±1.41 |
2.19±1.38 |
.110 |
|
KOA, n (%) |
561 (55.8) |
836 (69.0) |
<.001 |
1,047 (61.6) |
350 (67.6) |
.014 |
|
Laboratory parameters |
|
|
|
|
|
|
|
TG (mg/dL) |
111.6±54.1 |
169.6±104.1 |
<.001 |
138.1±88.1 |
160.1±93.7 |
<.001 |
|
TC (mg/dL) |
194.9±34.9 |
2,014.0±40.8 |
<.001 |
200.2±37.3 |
191.7±40.9 |
<.001 |
|
LDL-C (mg/dL) |
122.0±31.7 |
121.8±36.2 |
.890 |
124.2±32.5 |
114.4±38.5 |
<.001 |
|
HDL-C (mg/dL) |
50.6±11.3 |
45.3±10.2 |
<.001 |
48.4±10.9 |
45.3±11.0 |
<.001 |
In addition, with respect to type 2 diabetes mellitus status, the T2DM group showed significantly higher TyG-BMI (p <.001), body weight (p <.001), height (p =.002), body mass index (p <.001), waist circumference (p <.001), proportion of urban residence (p =.027), smoking (p =.009), knee osteoarthritis prevalence (p =.014), and triglyceride (p <.001) compared with the non-T2DM group, whereas total cholesterol (p <.001), low-density lipoprotein cholesterol (p <.001), and high-density lipoprotein cholesterol (p <.001)were significantly lower.
3. Comparison of variables according to physical activity levels
Table 3 presents the comparison of variables according to levels of light-intensity physical activity and moderate-to-vigorous physical activity. First, with respect to light-intensity physical activity, participants engaging in less than 150 minutes per week exhibited significantly higher age ( p<.001), KL grade ( p<.001), knee osteoarthritis prevalence ( p<.001), triglyceride levels ( p =.048), and TyG-BMI ( p =.046) than those engaging in 150 minutes or more per week, whereas moderate-to-vigorous physical activity time ( p =.004), height ( p <.001), education level ( p <.001), proportion of urban residence ( p <.001), energy intake ( p =.009), menopause age ( p =.002), and high-density lipoprotein cholesterol ( p <.001) were significantly lower.
Table 3.
Descriptive statistics of measured parameters according to LPA and MVPA
|
Variables |
LPA |
p-value |
MVPA |
p-value |
|
≥150 min/week (n=963/43.4%) |
<150 min/week (n=1,254/56.6%) |
≥150 min/week (n=457/20.6%) |
<150 min/week (n=1,760/79.4%) |
|
LPA (min/week) |
377.3±239.3 |
41.8±50.4 |
<.001 |
227.5±237.9 |
177.1±229.7 |
<.001 |
|
MVPA (min/week) |
154.6±320.1 |
115.5±307.8 |
.004 |
607.2±436.8 |
9.3±28.5 |
<.001 |
|
Age (year) |
71.1±4.5 |
72.4±4.7 |
<.001 |
71.2±4.4 |
72.0±4.7 |
<.001 |
|
Body weight (kg) |
55.8±8.0 |
55.5±9.1 |
.434 |
55.9±8.6 |
55.6±8.7 |
.419 |
|
Height (cm) |
151.8±5.6 |
150.8±5.7 |
<.001 |
151.7±5.4 |
151.1±5.8 |
.044 |
|
BMI (kg/m2) |
24.2±2.9 |
24.3±3.4 |
.187 |
24.2±3.1 |
24.3±3.2 |
.776 |
|
WC (cm) |
82.8±8.6 |
83.4±9.6 |
.104 |
83.0±8.9 |
83.1±9.2 |
.792 |
|
Socio-economic status |
|
|
|
|
|
|
|
Household income (10,000 won/month) |
186.4±230.1 |
169.4±226.5 |
.081 |
172.0±218.6 |
178.0±230.7 |
.615 |
|
Education, n (%) |
|
|
<.001 |
|
|
.786 |
|
Lower than elementary |
731 (75.9) |
1,078 (86.0) |
|
371 (81.2) |
1,438 (81.7) |
|
|
Middle/high |
206 (21.4) |
162 (12.9) |
|
76 (16.6) |
292 (16.6) |
|
|
Over than college |
26 (2.7) |
14 (1.1) |
|
10 (2.2) |
30 (1.7) |
|
|
Marital status, n (%) |
|
|
.786 |
|
|
.002 |
|
Married |
494 (51.3) |
636 (50.7) |
|
263 (57.5) |
867 (49.3) |
|
|
Unmarried/widowed/divorced |
469 (48.7) |
618 (49.3) |
|
194 (42.5) |
893 (50.7) |
|
|
Region, n (%) |
|
|
<.001 |
|
|
<.001 |
|
Urban |
714 (74.1) |
755 (60.2) |
|
270 (59.1) |
1,199 (68.1) |
|
|
Rural |
249 (25.9) |
499 (39.8) |
|
187 (40.9) |
561 (31.9) |
|
|
Health related parameters |
|
|
|
|
|
|
|
Smoking, n (%) |
65 (6.7) |
99 (7.9) |
.307 |
30 (6.6) |
134 (7.6) |
.445 |
|
Binge drinking, n (%) |
16 (1.7) |
14 (1.4) |
.668 |
6 (1.3) |
28 (1.6) |
.667 |
|
Energy intake (g/day) |
1,518.1±552.0 |
1,457.8±529.6 |
.009 |
1,501.5±553.4 |
1,479.5±536.7 |
.437 |
|
Menopause age (year) |
49.0±5.4 |
48.3±5.5 |
.002 |
48.6±5.5 |
48.6±5.5 |
.912 |
|
Hypertension, n (%) |
330 (34.3) |
404 (32.2) |
.301 |
145 (31.7) |
589 (33.5) |
.712 |
|
Type 2 Diabetes Mellitus, n (%) |
293 (23.4) |
225 (23.4) |
.999 |
409 (23.2) |
109 (23.9) |
.783 |
|
KL grade |
1.94±1.38 |
2.23±1.40 |
<.001 |
2.07±1.4 |
2.11±1.4 |
.595 |
|
KOA, n (%) |
566 (58.8) |
831 (66.3) |
<.001 |
283 (61.9) |
1,114 (63.3) |
.589 |
|
Laboratory parameters |
|
|
|
|
|
|
|
FBG (mg/dL) |
101.9±21.0 |
103.2±24.5 |
.192 |
103.1±22.4 |
102.5±23.2 |
.598 |
|
TG (mg/dL) |
139.0±79.1 |
146.6±97.3 |
.048 |
136.8±74.4 |
144.9±93.4 |
.084 |
|
TC (mg/dL) |
198.6±36.3 |
198.0±39.8 |
.689 |
196.3±36.7 |
198.7±38.7 |
.227 |
|
LDL-C (mg/dL) |
121.9±33.6 |
121.8±34.7 |
.938 |
120.6±34.3 |
122.2±34.2 |
.369 |
|
HDL-C (mg/dL) |
48.9±11.3 |
46.8±10.7 |
<.001 |
48.4±11.5 |
47.5±10.9 |
.158 |
|
TyG-BMI |
113.9±16.2 |
115.4±18.6 |
.046 |
114.2±16.9 |
114.9±17.8 |
.418 |
In addition, with respect to moderate-to-vigorous physical activity, participants engaging in less than 150 minutes per week showed significantly higher age (p <.001) and proportion of urban residence (p <.001) compared with those engaging in 150 minutes or more per week, whereas light-intensity physical activity time (p <.001), height (p =.044), and proportion of married individuals (p =.002) were significantly lower.
4. Risk of knee osteoarthritis according to insulin resistance, type 2 diabetes mellitus, and physical activity levels
Table 4 presents the estimated risk of knee osteoarthritis according to insulin resistance status, type 2 diabetes mellitus status, and levels of light-intensity and moderate-to-vigorous physical activity. First, with respect to insulin resistance status, in the unadjusted Model 1 (OR=1.768, 95% CI=1.486–2.105, p <.001), the Abnormal group showed a significantly higher risk of knee osteoarthritis compared with the Normal group (OR=1, reference), and this association remained significant in Model 2 adjusted for age (OR=1.852, 95% CI=1.553–2.209, p <.001) and in Model 3 additionally adjusted for waist circumference, monthly household income, educational level, marital status, residential area, smoking, binge drinking, energy intake, menopause age, and hypertension (OR=1.893, 95% CI=1.583–2.262, p <.001). Similarly, with respect to type 2 diabetes mellitus status, the T2DM group demonstrated a significantly higher risk of knee osteoarthritis than the non-T2DM group (OR=1, reference) across all models (Model 1: OR=1.311, 95% CI= 1.054–1.631, p =.014; Model 2: OR=1.332, 95% CI=1.069–1.659, p =.011; Model 3: OR=1.330, 95% CI=1.066–1.660, p =.012).
Table 4.
OR and 95% CI for knee osteoarthritis by glucose metabolism status, and physical activity
|
Model 1 |
Model 2 |
Model 3 |
|
OR (95% CI) |
p-value |
OR (95% CI) |
p-value |
OR (95% CI) |
p-value |
|
Glucose metabolism status |
|
|
|
|
|
|
|
Insulin resistance status |
|
|
|
|
|
|
|
Normal |
1 (reference) |
|
1 (reference) |
|
1 (reference) |
|
|
Abnormal |
1.768 (1.486-2.105) |
<.001 |
1.852 (1.553-2.209) |
<.001 |
1.893 (1.583-2.262) |
<.001 |
|
Type 2 Diabetes Mellitus |
|
|
|
|
|
|
|
Non-T2DM |
1 (reference) |
|
1 (reference) |
|
1 (reference) |
|
|
T2DM |
1.311 (1.054-1.631) |
.014 |
1.332 (1.069-1.659) |
.011 |
1.330 (1.066-1.660) |
.012 |
|
Physical activity |
|
|
|
|
|
|
|
LPA |
|
|
|
|
|
|
|
≥150 min/week |
1 (reference) |
|
1 (reference) |
|
1 (reference) |
|
|
<150 min/week |
1.378 (1.158-1.639) |
<.001 |
1.334 (1.120-1.589) |
.001 |
1.298 (1.087-1.551) |
.004 |
|
MVPA |
|
|
|
|
|
|
|
≥150 min/week |
1 (reference) |
|
1 (reference) |
|
1 (reference) |
|
|
<150 min/week |
1.060 (0.858-1.311) |
.589 |
1.027 (0.829-1.271) |
.809 |
1.027 (0.828-1.275) |
.805 |
Next, with respect to physical activity levels, participants engaging in less than 150 minutes per week of light-intensity physical activity exhibited a significantly higher risk of knee osteoarthritis compared with those engaging in 150 minutes or more per week (OR=1, reference) across all models (Model 1: OR=1.378, 95% CI=1.158–1.639, p <.001; Model 2: OR=1.334, 95% CI=1.120–1.589, p =.001; Model 3: OR=1.298, 95% CI=1.087–1.551, p =.004). However, no significant differences were observed between groups in the analysis of moderate-to-vigorous physical activity.
5. Risk of knee osteoarthritis by disease severity according to light-intensity physical activity within insulin resistance and type 2 diabetes mellitus groups
Table 5 presents the estimated risk of knee osteoarthritis according to light-intensity physical activity levels within the insulin resistance and type 2 diabetes mellitus groups. First, within the insulin resistance group, participants engaging in less than 150 minutes per week of light-intensity physical activity showed a significantly higher risk of knee osteoarthritis compared with those engaging in 150 minutes or more per week (OR=1, reference) in the unadjusted Model 1 (OR=1.460, 95% CI=1.142–1.866, p =.003), the age-adjusted Model 2 (OR=1.422, 95% CI=1.111–1.820, p =.005), and Model 3 additionally adjusted for waist circumference, monthly household income, educational level, marital status, residential area, smoking, binge drinking, energy intake, menopause age, and hypertension (OR=1.396, 95% CI=1.084–1.798, p =.010). Furthermore, in the analysis estimating the risk of progression from normal status to moderate-to-severe knee osteoarthritis, participants engaging in less than 150 minutes per week of light-intensity physical activity consistently demonstrated a significantly higher risk than those engaging in 150 minutes or more per week (OR=1, reference) across all models (Model 1: OR=1.554, 95% CI=1.201–2.010, p <.001; Model 2: OR=1.505, 95% CI=1.161–1.951, p =.002; Model 3: OR=1.490, 95% CI=1.141–1.944, p =.003).
Table 5.
OR and 95% CI for knee osteoarthritis by LPA among individuals with insulin resistance and type 2 diabetes mellitus
|
Model 1 |
Model 2 |
Model 3 |
|
OR (95% CI) |
p-value |
OR (95% CI) |
p-value |
OR (95% CI) |
p-value |
|
Insulin resistance status |
|
|
|
|
|
|
|
Abnormal |
|
|
|
|
|
|
|
Normal vs. Overall KOA |
|
|
|
|
|
|
|
≥150 min/week |
1 (reference) |
|
1 (reference) |
|
1 (reference) |
|
|
<150 min/week |
1.460 (1.142-1.866) |
.003 |
1.422 (1.111-1.820) |
.005 |
1.396 (1.084-1.798) |
.010 |
|
Normal vs. Light KOA |
|
|
|
|
|
|
|
≥150 min/week |
1 (reference) |
|
1 (reference) |
|
1 (reference) |
|
|
<150 min/week |
1.188 (0.837-1.687) |
.334 |
1.174 (0.826-1.668) |
.371 |
1.149 (0.801-1.649) |
.450 |
|
Normal vs. Moderate or Severe KOA |
|
|
|
|
|
|
|
≥150 min/week |
1 (reference) |
|
1 (reference) |
|
1 (reference) |
|
|
<150 min/week |
1.554 (1.201-2.010) |
<.001 |
1.505 (1.161-1.951) |
.002 |
1.490 (1.141-1.944) |
.003 |
|
Type 2 Diabetes Mellitus |
|
|
|
|
|
|
|
T2DM |
|
|
|
|
|
|
|
Normal vs. Overall KOA |
|
|
|
|
|
|
|
≥150 min/week |
1 (reference) |
|
1 (reference) |
|
1 (reference) |
|
|
<150 min/week |
1.390 (0.936-2.063) |
.102 |
1.287 (0.863-1.920) |
.216 |
1.232 (0.815-1.861) |
.322 |
|
Normal vs. Light KOA |
|
|
|
|
|
|
|
≥150 min/week |
1 (reference) |
|
1 (reference) |
|
1 (reference) |
|
|
<150 min/week |
1.094 (0.657-1.822) |
.730 |
1.012 (0.601-1.702) |
.966 |
0.982 (0.565-1.705) |
.948 |
|
Normal vs. Moderate or Severe KOA |
|
|
|
|
|
|
|
≥150 min/week |
1 (reference) |
|
1 (reference) |
|
1 (reference) |
|
|
<150 min/week |
1.739 (1.173-2.578) |
.006 |
1.598 (1.072-2.383) |
.021 |
1.441 (0.954-2.177) |
.083 |
Next, within the type 2 diabetes mellitus group, the analysis of knee osteoarthritis risk according to light-intensity physical activity levels revealed no statistically significant differences overall. However, in the se-verity-specific analysis, participants engaging in less than 150 minutes per week of light-intensity physical activity exhibited a significantly higher risk of progression from normal status to moderate-to-severe knee osteoarthritis compared with those engaging in 150 minutes or more per week (OR=1, reference) in the unadjusted Model 1 (OR=1.739, 95% CI=1.173–2.578, p =.006) and the age-adjusted Model 2 (OR=1.598, 95% CI=1.072–2.383, p =.021).
DISCUSSION
In this study, the associations among insulin resistance, type 2 diabetes mellitus, physical activity, and knee osteoarthritis were examined in older women, and the results showed that the group with abnormal insulin resistance exhibited a significantly higher risk of knee osteoarthritis compared with the normal group, while the group with type 2 diabetes mellitus also demonstrated a significantly higher risk of knee osteoarthritis compared with the non-diabetic group. In addition, the group engaging in less than 150 minutes per week of light-intensity physical activity showed a significantly higher risk of knee osteoarthritis compared with the group engaging in 150 minutes or more per week. Finally, in the analysis of stage-specific knee osteoarthritis risk according to light-intensity physical activity levels within the insulin resistance and type 2 diabetes mellitus groups, participants engaging in less than 150 minutes per week exhibited a significantly higher risk of progression from normal status to moderate-to-severe knee osteoarthritis compared with those engaging in 150 minutes or more per week.
Estrogen, a hormone known to play a critical role in female physiology, has been reported to exert a protective effect against knee joint degeneration by inhibiting extracellular matrix–degrading factors that are essential for maintaining the structural integrity and functional capacity of the knee joint, as well as by promoting the synthesis of collagen and proteoglycans within the cartilage matrix, thereby delaying the progression of knee osteoarthritis [ 29]. In addition, recent studies have demonstrated sex-specific differences in gene expression patterns and disease progression in osteoarthritis, with evidence indicating that postmenopausal reductions in estrogen levels exert a greater influence on osteoarthritis progression in women than in men [ 30]. Accordingly, postmenopausal women represent a population particularly vulnerable to knee osteoarthritis, and given the absence of definitive therapeutic options for knee osteoarthritis, there is a pressing need for focused research aimed at identifying effective preventive and management strategies.
Insulin resistance is widely recognized as a common underlying factor in various chronic diseases, including cardiovascular and metabolic disorders, and has recently been reported to be associated with the development of knee osteoarthritis, one of the most prevalent musculoskeletal conditions associated with aging [ 7, 8, 31]. Specifically, in addition to the association between insulin and chondrocyte function described in the Introduction, insulin has been shown to promote anabolic processes in articular cartilage by inhibiting the actions of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) [ 7, 8], while increases in free fatty acids resulting from insulin resistance have been demonstrated to contribute to catabolic processes within cartilage tissue.
As a result, insulin resistance and type 2 diabetes mellitus have emerged as major risk factors for knee osteoarthritis [ 31]. Indeed, numerous epidemiological studies have reported that increased insulin resistance and type 2 diabetes mellitus are associated with an elevated risk of knee osteoarthritis [ 11, 32, 33], and consistent with these findings, the present study demonstrated that both TyG-BMI, a surrogate marker of insulin resistance, and the presence of type 2 diabetes mellitus were associated with a significantly higher risk of knee osteoarthritis compared with normal groups among older women. These findings support previous studies reporting that insulin resistance and type 2 diabetes mellitus may act as independent risk factors for knee osteoarthritis and suggest the need for an integrated approach that incorporates metabolic health considerations when developing strategies for the prevention of knee osteoarthritis. However, due to the cross-sectional design of this study, the possibility of reverse causality, whereby increased insulin resistance and type 2 diabetes mellitus may be consequences rather than causes of knee osteoarthritis, cannot be excluded, and therefore further validation through longitudinal study designs is warranted.
In addition, the group engaging in less than 150 minutes per week of light-intensity physical activity showed a significantly higher risk of knee osteoarthritis compared with the group engaging in 150 minutes or more per week. Consistent with these findings, large-scale prospective cohort studies based on population data from the United Kingdom and the United States have reported that regular walking activity after midlife may contribute to the prevention of knee osteoarthritis [ 17, 18], and another cohort study examining associations between various types of physical activity and knee osteoarthritis identified light-intensity physical activity as a potential protective factor for the prevention of knee osteoarthritis [ 34]. Taken together, these findings suggest that light-intensity physical activity may serve as an effective intervention for the prevention and management of knee osteoarthritis among older adults, although further studies are needed to establish evidence-based exercise guidelines by identifying optimal walking frequency and duration for
Finally, in the present study, the analysis of knee osteoarthritis risk according to light-intensity physical activity levels within the insulin resistance and type 2 diabetes mellitus groups revealed that in both groups, participants engaging in less than 150 minutes per week had a significantly higher risk of progression from normal status to moderate-to-severe knee osteoarthritis compared with those engaging in 150 minutes or more per week. These findings are consistent with previous studies suggesting that light-intensity physical activity may serve as an effective strategy for the prevention of knee osteoarthritis by promoting weight reduction and increases in muscle strength among overweight and obese individuals, as well as by improving synovial fluid circulation within the joint and enhancing nutrient supply to articular cartilage and synovial tissue [ 35]. Notably, the present study extends the existing literature by moving beyond prior research that primarily focused on the general older adult population and instead identifying high-risk groups with insulin resistance and type 2 diabetes mellitus, thereby demonstrating the protective effect of light-intensity physical activity against progression from normal knee joint status to severe disease.
These results suggest that light-intensity physical activity may represent a feasible, safe, and effective strategy for the prevention of knee osteoarthritis among older women with impaired glucose metabolism.
Meanwhile, the absence of significant differences in knee osteoarthritis risk according to moderate-to-vigorous physical activity levels observed in this study may be explained by several factors. First, the physical activity questionnaire used in this study assessed physical activity intensity without distinguishing among activity domains such as occupational, leisure-time, or transportation-related activity. While leisure-time moderate-to-vigorous physical activity has been reported as a protective factor for knee osteoarthritis and occupational moderate-to-vigorous physical activity has been reported as a risk factor, the inability to differentiate activity domains in this study may have resulted in opposing effects offsetting one another [ 36, 37].
Overall, although this study identified the benefits of light-intensity physical activity in the relationship between insulin resistance, type 2 diabetes mellitus, and knee osteoarthritis based on a large, nationally representative epidemiological dataset, several limitations should be acknowledged. First, due to the cross-sectional study design, causal relationships among the study variables cannot be established. Thus, longitudinal studies are required. Second, the study population was limited to older women, which restricts the generalizability of the findings, high-lighting the need for future studies including diverse sexes and age groups. Third, insulin resistance was assessed using a surrogate marker, and physical activity was assessed using a questionnaire-based method, indicating the need for future studies employing objective measurement techniques. Fourth, due to the characteristics of the survey design, information on medication use and history of knee replacement surgery, which may influence knee osteoarthritis, could not be assessed, and the potential impact of these factors on the results cannot be excluded. Fifth, although knee pain severity may influence participation in physical activity, this factor could not be accounted for in the present study. Sixth, the study utilized data collected over a relatively long period in the past, and therefore may not fully reflect recent demographic changes. Accordingly, future studies addressing these limitations through interventional and longitudinal designs that include diverse populations are needed to more clearly elucidate the associations among insulin resistance, type 2 diabetes mellitus, physical activity, and knee osteoarthritis.
CONCLUSION
Based on a large, nationally representative epidemiological survey, this study examined the associations among insulin resistance type 2 diabetes mellitus, physical activity, and knee osteoarthritis in older women and demonstrated that engaging in at least 150 minutes per week of light-intensity physical activity may play a protective role in the prevention of knee osteoarthritis among older women with insulin resistance and type 2 diabetes mellitus. These findings suggest that regular participation in light-intensity physical activity for 150 minutes or more per week may serve as a practical and effective strategy for the prevention of knee osteoarthritis in older women with impaired glucose metabolism.
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|