Type 2 diabetes is associated with low muscle mass in older adults

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1 bs_bs_banner Geriatr Gerontol Int 2014; 14 (Suppl. 1): ORIGINAL ARTICLE Type 2 is associated with low muscle mass in older adults Kyung-Soo Kim, 1 Kyung-Sun ark, 2 Moon-Jong Kim, 3 Soo-Kyung Kim, 1 Yong-Wook Cho 1 and Seok Won ark 1 1 Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, 2 Department of Internal Medicine, Onnuri Hospital, Incheon, and 3 Department of Family Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea Aims: Our aim was to clarify the association between type 2 and the risk of low muscle mass in older adults. Methods: In the present study, 414 adults aged 65 years or older (144 patients with type 2 and 270 control participants) were included. Body composition was measured by dual-energy X-ray absorptiometry. Low muscle mass was defined as the appendicular skeletal muscle mass/height 2 (ASM/Ht 2 ) or appendicular skeletal muscle mass/weight (ASM/Wt) of <2 SD below the sex-specific normal mean of the young reference group, or <lower 20th percentile of total body skeletal muscle mass/weight (TSM/Wt) from control participants. Results: Older men with type 2 showed significantly lower appendicular skeletal muscle mass than those without (19.5 ± 3.5 kg vs 21.0 ± 2.8 kg, < 0.001). The prevalence of low muscle mass was consistently higher in older men with than those without defined by ASM/Ht 2 (57.6% vs 41.5%, = 0.040), ASM/Wt (23.7% vs 12.3%, = 0.046) and TSM/Wt (49.2% vs 20.0%, < 0.001). In older women with, the prevalence of low muscle mass was higher than those without by ASM/Wt (25.9% vs 15.0%, = 0.044) and TSM/Wt (32.9% vs 20.0%, = 0.030), but not by ASM/Ht 2 (7.1% vs 8.6%, = 0.685). The risk of low muscle mass was approximately two- to fourfold higher in older adults with type 2, even after adjusting for age, body mass index, current smoking and other risk factors. Conclusions: In Korean older adults, type 2 is associated with low muscle mass. Geriatr Gerontol Int 2014; 14 (Suppl. 1): Keywords: elderly, sarcopenia, type 2. Introduction Accepted for publication 1 October Correspondence: Dr Seok Won ark MD hd DrH, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam-si, Gyeonggi-do , Korea. spark@cha.ac.kr The industrialized countries, including Korea, are rapidly aging. 1,2 Estimates by the World Health Organization suggest that there were 600 million people aged 60 years or older in the year 2000, and that this number will increase to 1.2 billion by the year Aging results in a change of body composition, such as a progressive loss of muscle mass and gain of fat mass. 4 Sarcopenia is the age-related decline in muscle mass, and is associated with increased disability and mortality. 5 7 As muscle is not only responsible for physical strength, stamina and balance, but also metabolically active tissue, sarcopenia might affect quality of life, the need for supportive services and contribute to the development of metabolic disorders. 5,8 10 Although the International Working Group on Sarcopenia (IWGS) and the European Working Group on Sarcopenia in Older eople (EWGSO) included measurements of physical performance and/or muscle strength in defining sarcopenia, earlier definitions focused on measurements of low muscle mass only. 11 Within the existing literature, which defined sarcopenia by low muscle mass, the prevalence of sarcopenia in adults aged years is in the range of 5 13%. These prevalence estimates increase to 11 50% for the population aged 80 years or older. 12 Conservative estimates based on the prevalence of sarcopenia and World Health Organization population data suggest that sarcopenia affects more than 50 million people today, and that it will affect more than 200 million people over the next 40 years Japan Geriatrics Society doi: /ggi

2 K-S Kim et al. Most individuals with are obese and have bigger muscle mass, so we could think that they might have enough muscle mass to prevent sarcopenia with aging. Actually, in the Health, Aging, and Body composition Study (Health ABC), older adults with type 2 had a greater muscle mass in their arms and legs than those without. 14 However, in older adults, type 2 is associated with excessive loss of skeletal muscle mass, as well as lower muscle quality and strength Meanwhile, the Asian population is thin, and has a different body composition compared with their Western counterparts. Only a few studies have examined the effect of type 2 on the change of body composition and the prevalence of low muscle mass in Asian older adults. To clarify the association between type 2 and the risk of low muscle mass in Asian older adults, we evaluated the body composition and the prevalence of low muscle mass defined by different indices, including appendicular skeletal muscle mass mass/height 2 (ASM/Ht 2 ), appendicular skeletal muscle mass/weight (ASM/Wt), and total body skeletal muscle mass/weight (TSM/Wt) in Korean older adults with and without type 2. Methods Study participants In the present study, we enrolled 144 consecutive patients with type 2 who visited the clinic at the CHA Bundang Medical Center, Seongnam, Korea. We also enrolled 270 participants without type 2 among those who underwent a general health check-up at the same institution. All participants were aged 65 years or older in the recruitment period from December 2008 to January We excluded participants who had type 1, acute disease, known liver or kidney disease, history of stroke, angina, myocardial infarction or cancer. Medical histories and lifestyle information were collected through personal interview. articipants were considered to have type 2 if they had: (i) a report of having the diagnosis of with onset after age 25 years; (ii) current use of oral hypoglycemic medications or insulin; or (iii) a fasting plasma glucose concentration 126 mg/dl at baseline. The present study was approved by the CHA University Institutional Review Board, and informed consent was obtained from all study participants. Clinical and laboratory measurements Body weight and height were measured in participants wearing a hospital gown and without shoes on a calibrated balance beam scale and stadiometer, respectively. Waist circumference was measured at the midpoint between the lower border of the rib cage and the iliac crest. Blood pressure was measured using a mercury sphygmomanometer while the participants were seated. All blood samples were obtained in the morning after overnight fasting and were immediately analyzed for fasting plasma glucose. Serum total cholesterol, triglyceride and high-density lipoprotein (HDL) cholesterol levels were determined enzymatically. Low-density lipoprotein (LDL) cholesterol level was calculated according to the Friedewald formula. Body composition We used fan-beam dual energy X-ray absorptiometry (DXA; Discovery-W, Hologic, Bedford, MA, USA) to measure total body mass and body composition. Appendicular skeletal muscle mass (ASM) was obtained by summing up lean soft tissue (non-fat, non-bone) mass in the arms and legs, which represents primarily skeletal muscle mass in the extremities. Definitions of low muscle mass We used three definitions for low muscle mass: the first method was ASM divided by height squared (ASM/Ht 2 ; kg/m 2 ) less than 2 standard deviations (SD) below the sex-specific normal mean of the young reference group. 17 The cut-off values for low muscle mass were 7.40 kg/m 2 in men and 5.14 kg/m 2 in women by using ASM/Ht Because ASM/Ht 2 is highly correlated with body mass index (BMI), this method identifies most thin people as having sarcopenia. Therefore, the ASM/Ht 2 criteria could have limited value to identify sarcopenia in overweight or obese subjects. To overcome this limitation, we used weight-adjusted sarcopenic indices. The second definition was ASM as a percentage of body weight (ASM/Wt) less than 2 SD below the sex-specific normal mean of the young reference group. 5 The cutoff value for low muscle mass was 29.5% in men and 23.2% in women. 19 The last definition was obtained by converting the total body skeletal muscle mass to a percentage of body weight (TSM/Wt). 5 With this method, we defined low muscle mass as the lowest quintile of TSM/Wt from participants without type 2. The cut-off values for TSM/Wt were 34.9% in men and 25.8% in women. Statistical analysis Data for continuous variables are presented as the means ± SD, and categorical variables are reported as percentages. The participants characteristics and body composition were compared according to status using independent-sample t-tests for continuous measures and χ 2 -tests for categorical measures. The prevalence of low muscle mass according to the three different methods was also compared. Multivariate Japan Geriatrics Society

3 Low muscle mass in older adults with type 2 logistic regression models were used to estimate the odds ratio (OR) and 95% confidence intervals (CI) for low muscle mass in patients with. The regression models were developed to adjust for age, BMI, current smoking, blood pressure (systolic and diastolic) and lipid levels (total cholesterol, triglyceride, HDL cholesterol). A -value <0.05 was considered significant. All statistical analyses were carried out by using IBM SSS Statistics (version 19.0; IBM, Somers, NY, USA). Results Table 1 shows the clinical and biochemical characteristics of the study population. There was no significant difference in age, BMI, waist circumference, systolic blood pressure and triglyceride levels between older adults with or without. In men, older adults with type 2 took more statins than those without. Older women with type 2 took more antihypertensive medications and statins than those without. The average duration of type 2 was 10.7 years in men and 13.0 years in women from the time of diagnosis; the mean glycated hemoglobin was 8.2% in men and 8.5% in women. Older men with showed significantly lower ASM than those without (19.5 ± 3.5 kg vs 21.0 ± 2.8 kg, < 0.001). In women, ASM, total body fat and regional fat mass were not different between older adults with and without. Sarcopenic indices, such as ASM/Ht 2, ASM/Wt and TSM/Wt, were significantly lower in older adults with than those without, except for ASM/Ht 2 in women (Table 2). The prevalence of low muscle mass was higher in older men with than those without (57.6% vs 41.5%, = 0.040), but not in women (7.1% vs 8.6%, = 0.685) by the ASM/Ht 2 method (Table 3). When we used the ASM/Wt method, the prevalence of low muscle mass was approximately twofold higher in older adults with than those without (23.7% vs 12.3% in men, = 0.046; 25.9% vs 15.0% in women, = 0.044). By the TSM/Wt method, the prevalence of low muscle mass was also higher in older adults with than those without (49.2% vs 20.0% in men, < 0.001; 32.9% vs 20.0% in women, = 0.030). The associations between type 2 and low muscle mass defined by various indices are shown in Table 4. Type 2 was associated with a higher prevalence of low muscle mass in older adults according to various methods (OR = in men, in women) except for ASM/Ht 2 in women. Even after adjustment for age, BMI, current smoking, blood pressure (systolic and diastolic) and lipid levels, older men with type 2 had a two- to fourfold increased Table 1 Clinical and biochemical characteristics of the study participants by status, according to sex Male Female With Without With Without (n = 59) (n = 130) (n = 85) (n = 140) Age (years) 71.3 ± ± ± ± Height (cm) ± ± ± ± Weight (kg) 63.8 ± ± ± ± Body mass index (kg/m 2 ) 23.6 ± ± ± ± Waist circumference (cm) 86.6 ± ± ± ± Systolic blood pressure (mmhg) ± ± ± ± Diastolic blood pressure (mmhg) 75.9 ± ± ± ± 9.9 <0.001 Total cholesterol (mg/dl) ± ± 35.0 < ± ± 33.9 <0.001 Triglyceride (mg/dl) ± ± ± ± HDL cholesterol (mg/dl) 44.9 ± ± ± ± LDL cholesterol (mg/dl) 92.6 ± ± 30.6 < ± ± 31.3 <0.001 Fasting plasma glucose (mg/dl) ± ± 12.5 < ± ± 13.9 <0.001 HbA1c (%) 8.2 ± ± 2.3 Diabetes duration (years) 10.7 ± ± 8.9 Current smoking (%) Anti-hypertensive medications (%) <0.001 Statins (%) < <0.001 Data are expressed as the mean ± standard deviation or %. HbA1c, glycated hemoglobin; HDL, high-density lipoprotein; LDL, low-density lipoprotein Japan Geriatrics Society 117

4 K-S Kim et al. Table 2 Comparison of body composition and sarcopenic indices by status, stratified by sex Male Female With Without With Without (n = 59) (n = 130) (n = 85) (n = 140) Total body skeletal muscle mass (kg) 47.2 ± ± ± ± Trunk lean mass (kg) 24.1 ± ± ± ± 2.2 <0.001 Appendicular skeletal muscle mass (kg) 19.5 ± ± ± ± Total body fat mass (kg) 14.9 ± ± ± ± Trunk fat mass (kg) 7.8 ± ± ± ± Appendicular fat mass (kg) 5.4 ± ± ± ± Appendicular skeletal muscle 7.2 ± ± ± ± mass/height 2 (kg/m 2 ) Appendicular skeletal muscle 30.7 ± ± 2.6 < ± ± mass/weight (%) Total body skeletal muscle mass/weight (%) 34.9 ± ± 3.0 < ± ± Data are expressed as the mean ± standard deviation or %. Table 3 revalence of low muscle mass using the different indices, stratified by sex With Male Without With Female Without Definition Definition Definition < Data are expressed as %. Definition 1: Appendicular skeletal muscle mass / height 2 <2SD below the mean of the young reference group (male <7.40 kg/m 2, female <5.14 kg/m 2 ). Definition 2: Appendicular skeletal muscle mass / weight <2SD below the mean of the young reference group (male <29.5%, female <23.2%). Definition 3: Total body skeletal muscle mass / weight below lowest quintile cut-point value of the participants without (male <34.9%, female <25.8%). risk of low muscle mass (OR ). In older women, multiple adjustments for the aforementioned factors attenuated the association between type 2 and low muscle mass (OR ). Discussion In the present study, older men with type 2 had a lower ASM than those without type 2, even though they had similar BMI. Furthermore, both older men and women with type 2 showed a higher prevalence of low muscle mass by using three different methods (ASM/Ht 2, ASM/Wt and TSM/Wt) than their non-diabetic counterparts. Sarcopenia is commonly observed in older adults as a result of age-related loss of muscle mass. Most individuals with type 2 are generally more obese and have bigger muscle mass than those without type 2 in Western countries. 20 In a cross-sectional analysis of the Health ABC study, patients with type 2 showed increases in both lean body mass and body fat mass compared with subjects without. 14 However, the present study reported that older adults with type 2 had either smaller (men) or not larger (women) muscle mass than those without type 2. This is the first study showing that older adults with type 2 had lower muscle mass compared with those without type 2 in Asia. The discrepancy between Asian and Western studies might originate from ethnic differences in the characteristics of type 2. In Western populations, despite the larger muscle mass, muscle quality was consistently lower in older adults with type 2, regardless of sex and muscle groups examined (arm or leg). 14 In community-dwelling older adults, type 2 is also associated with slower walking speed and reduced lower-limb muscle density, strength, and quality. 7 Furthermore, type 2 is associated with accelerated loss of leg muscle Japan Geriatrics Society

5 Low muscle mass in older adults with type 2 Table 4 Association between status and low muscle mass defined by various indices, stratified by sex Definition 1 Definition 2 Definition 3 OR (95% CI) OR (95% CI) OR (95% CI) Men Unadjusted 1.91 ( ) ( ) ( ) <0.001 Model ( ) ( ) ( ) <0.001 Model ( ) ( ) ( ) <0.001 Model ( ) ( ) ( ) <0.001 Women Unadjusted 0.81 ( ) ( ) ( ) Model ( ) ( ) ( ) Model ( ) ( ) ( ) Model ( ) ( ) ( ) Definition 1: Appendicular skeletal muscle mass / height 2 <2SD below the mean of the young reference group (male <7.40 kg/m 2, female <5.14 kg/m 2 ). Definition 2: Appendicular skeletal muscle mass / weight <2SD below the mean of the young reference group (male <29.5%, female <23.2%). Definition 3: Total body skeletal muscle mass / weight below lowest quintile cut-point value of the subjects without (male <34.9%, female <25.8%). Model 1: Adjusted for age. Model 2: Additionally adjusted for body mass index. Model 3: Additionally adjusted for current smoking, blood pressure (systolic and diastolic) and lipid levels (total cholesterol, triglyceride, high-density lipoprotein cholesterol). CI, confidence interval; OR, odds ratio. strength and quality in older adults. 15,16 Unfortunately, we were not able to identify those associations, because we did not evaluate muscle strength and physical performance. However, unlike their Western counterparts, older adults with type 2 in Korea showed decreased muscle mass indices than those without type 2, therefore they might have reduced muscle quality and strength. It is generally accepted that muscle strength is as important as muscle mass, because muscle strength does not depend solely on muscle mass, and the relationship between strength and mass is not linear. 21,22 IWGS and EWGSO recommend that both low muscle mass and low muscle function (strength or performance) are required for the diagnosis of sarcopenia. 11,13 Although we evaluated only muscle mass indices by three different methods, the prevalence of sarcopenia or low muscle mass was higher in Korean older adults with type 2 compared with published results in white and Hispanic populations. 17,23,24 Furthermore, previous studies have shown that height-adjusted skeletal muscle index tended to identify low muscle mass in lean participants, and weight-adjusted skeletal muscle index tended to identify low muscle mass in overweight or obese participants. 11 Likewise, in the present study, low muscle mass defined by ASM/Ht 2 was more prevalent in lean people, whereas low muscle mass defined by ASM/Wt or TSM/Wt was more commonly observed in overweight and obese people (data not shown). The reason for a loss of muscle mass in older adults with type 2 is not clear. The cause of sarcopenia is generally thought to be multifactorial. Environmental factors, disease triggers, activation of inflammatory pathways, loss of neuromuscular junctions, reduced satellite cell numbers and hormonal changes are all thought to contribute. 25 Recent progress in the understanding of molecular pathways has helped to further highlight transforming growth factor-β signaling, apoptosis activation and declines in mitochondrial function as potentially important factors triggering sarcopenia. 8,26,27 In addition, anabolic hormones are important in the maintenance of muscle mass by activating the phosphotidyl-inositol-3-kinase-active human protein kinase system in the cell, and insulin resistance decreases the activity of this pathway. 28 A metabolic consequence of uncontrolled hyperglycemia is catabolism, which depending on the severity, is accompanied by muscle protein breakdown and inadequate energy use, potentially resulting in poor muscle function and decreased muscle mass. 29,30 It can be postulated that metabolic abnormalities in type 2 might negatively affect muscle mass. 31 Insulin resistance in type 2 also results in the reduced synthesis of whole-body proteins. 32 Further research is required to identify the mechanism for the rapid loss of skeletal muscle mass in older adults with type 2. The present study had several limitations that must be considered. First, there was no objective measure to estimate muscle strength and physical performance. Further studies are required to measure physical performance and/or muscle strength to estimate sarcopenia in accordance with the IWGS and EWGSO criteria. Second, this was a cross-sectional study showing only an association between type 2 and low muscle mass. We were not able to identify the factors associated with the loss of muscle mass in older adults with type Japan Geriatrics Society 119

6 K-S Kim et al., because the present study was not designed to examine the effect of glycemic control, specific treatments, other hormones and inflammatory cytokines. Third, the present study did not examine lifestyle factors, such as physical activity and nutritional status, which might have potential confounding effects on low muscle mass. Finally, the association between type 2 and low muscle mass was more strongly shown in men than women. One possible explanation is that older women with type 2 showed a tendency to have higher BMI than those without (24.5 ± 3.5 vs 23.8 ± 3.0). Although the difference was statistically not significant ( = 0.105), it might attenuate the association between type 2 and low muscle mass in women. In conclusion, the present study showed that in Korean older adults, type 2 was associated with low muscle mass. Disclosure statement The authors declare no conflict of interest. References 1 Kim KS, Kim SK, Sung KM, Cho YW, ark SW. 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