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1140808－肌少症的診斷與治療(醫師公會)－高雄榮民總醫院老年醫學中心.pdf
日期：114年8月8日 主題：老人衰弱及肌少症的診斷與治療 講師：王郁鈞醫師-高雄榮總老年醫學中心
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1140808－肌少症的診斷與治療(醫師公會)－高雄榮民總醫院老年醫學中心.pdf
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- 2. About me • 中國醫藥大學中醫系學士 •高雄醫學大學醫務管理暨醫療資訊學系碩士 • 日本東京大學老人醫學科研究訪問學者 • 台灣家庭醫學會專科醫師 • 台灣老年學暨老年醫學會專科醫師 • 高雄榮民總醫院高齡醫學中心主治醫師 • 教育部部定助理教授 • 台灣整合照護學會監事 • 高雄市長照推動小組委員 • 專長: 高齡整合照護, 衰弱症, 肌少症, 長期照護
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- 12. 衰弱的兩大操作型定義 • Physical frailty –slow walking speed – poor hand grip – exhaustion – weight loss – low energy intake • Outcome – fall – disability – hospitalization – death • Cumulative deficits – impairments in • cognition • mood • communication • mobility • balance • bowel and bladder function • nutrition • IADL/ADL • social resources • comorbidities • Outcome – death – institutionalization Fried LP, et al. J Gerontol 2001; 56A:M1–M11 Rockwood KC, et al. Lancet 1999;353:205-6 Jones DM, et al. JAGS 2004;52:1929-33
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- 14. Sarcopenia as a fundamentalcomponent of frailty Bauer J.M., et al. Exp Gerontol, 2008. 43(7): p. 674-8.
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- 18. Female gender Low birthrate Genetic susceptibility Increased muscle turnover Reduced number of muscle cells Hormonal deregulation Changes in nervous system Mitochondrial dysfunction Peripheral vascular flow Malnutrition Low protein intake Alcohol/ smoking Physical inactivity Cognitive impairment Mood disturbances Diabetes mellitus Heart / liver / lung / renal failure Osteoarthritis Chronic pain Drugs Starvation Bed rest /immobility /deconditioning Weightlessness Frailty and sarcopenia as the common phenotype of advanced biological aging Cruz-Jentoft AJ, et al. Curr Opin Clin Nutr Metab 2010;13:1-7 18
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- 20. Men Women Handgrip Strength (kg) GaitSpeed (m/s) Studenski S et al. JAMA. 2011 Jan 5;305(1):50-8.
- 21. Strength，not muscle mass, associatedwith mortality in Health ABC study Newman AB et. al. J Gerontol A Biol Sci Med Sci. 2006;61(1):72-7. Men, grip strength, and mortality. Women, grip strength, and mortality.
- 22. Sarcopenia ICD-10: M62.84 Age-related progressiveand generalized skeletal muscle disorder that involves the accelerated loss of muscle mass and function Cruz-Jentoft AJ, Sayer AA. Lancet. 2019;393(10191):2636-2646. 肌少症 22
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- 24. Low Muscle Mass Low muscle strength or/and Low physicalperformance Definition of Sarcopenia by AWGS 2019 24
- 25. Acute to chronic healthcare or clinical research sengs AWGS 2019: Identifying and diagnosing older adults with or at-risk for sarcopenia Primary health care Community preventive services settings Acute to chronic health care Clinical research settings 25
- 26. Primary Health Careor Community Preventive Services Settings 26
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- 28. Yubi-Wakka Test 28 Men <34cm Women < 33cm
- 29. Acute Health Careor Clinical Research Settings 29
- 30. Low Muscle Mass ASM/height2 byDXA and BIA < 7.0 kg/m2 for men (DXA/BIA) < 5.4 kg/m2 (by DXA) < 5.7 kg/m2 (by BIA) for women Low Muscle Strength By handgrip < 28 kg for men < 18 kg for women Low Physical Performance One of the following criteria • 6-meter walk speed <1.0 m/s • 5-time chair stand test ≥ 12 s • SPPB ≤ 9 or/ and Definition of Sarcopenia by AWGS 2019 Severe sarcopenia: low muscle mass + low muscle strength + low physical performance 30
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- 32. Demling RH. Eplasty.2009;9:65–94 Limited activities of daily living Lowered quality of life ● Decreased immunity ● Increased risk of infection ● Decreased wound healing ● Increased muscle weakness ● Increased risk of infection ● Too weak to sit ● Pressure ulcers ● Pneumonia ● Lack of healing ● Increased risk of death, usually from pneumonia % Loss of LBM Associated complications 肌少症對老年人的影響
- 33. Nathalia Perleberg Bachettiniet al. Eur J Clin Nutr. 2020 Apr;74(4):573-580. 肌少症增加死亡風險 1,292 noninstitutionalized subjects (>60 years); EWGSOP2 definition Prospective cohort study Severe Sarcopenia
- 34. Sarcopenia and 2-yearrisk of falls in a population of persons aged over 80(N=260 ) 25.4% participants diagnosed sarcopenia Prospective cohort study (ilSIRENTE Study) Risk of falling 3X Landi F et al. Clin Nutr. 2012 Oct;31(5):652-8 肌少症增加跌倒風險 After adjusting for age, gender, cognitive impairment, ADL impairment, sensory impairments, BMI, depression, physical activity, cholesterol, stroke, diabetes, number of medications, and C-reactive protein
- 35. 7 cross-sectional studies(5,994subjects) Meta-analysis OR: 2.246 Chang KV, et al. J Am Med Dir Assoc. 2016;17(12):1164.e7-1164.e15. 肌少症與認知功能
- 36. Yang CP, etal., Aging Cell 2020;19:e13107 肌肉退化影響大腦？
- 37. 台日共同驗證身智衰退症之臨床預後 Lee WJ, etal., PLoS One 2018;13:e0200447 Follow-up time (months) Dementia survival rates a b c d Shimada H, et al., J Clin Med 2019;7:E250
- 38. • Exercise intervention •Nutritional supplement • Medications(?) J Orthop Translat. 2020 Apr 30;23:38-52. 維持肌肉健康的方式
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- 40. resistance training programslasting > 8 week (>65 year old) diagnosed with (pre) sarcopenia and (pre) frailty Resistance Training on muscle mass and physical function Handgrip strength Lower-limb Strength Gait Speed Balance Muscle Mass Effective Size 95% CI 0.75 (95% CI :0.49-1.02) 0.29 (95% CI: 0.12- 0.46) 0.68 (95% CI: 0.23- 1.13) 0.93 (95% CI: 0.64- 1.22) 0.51 (95% CI: 0.23- 0.78) P Value 0.001 <0.001 <0.001 0.002 0.007 Meta-analysis (25 RCTs) J Clin Med. 2021 Apr 12;10(8):1630.
- 41. Experimental Gerontology 48(2013) 492–498 6-months resistance exercise training increase mainly on type II muscle fiber 26 healthy older men (age 71 ± 1 year)
- 42. 阻力型運動沒有年齡限制 • Increase sizeof both type I and type II muscle fibers • Improvements in muscle strength and size in healthy older people is similar to younger people • Even in very old nursing home residents, resistance exercise training showed improvements in muscle fiber CSA (3%–9%), muscle strength (> 100%) and physical performance such as gait speed and stair climbing 42 N Engl J Med. 1994;330:1769–1775 健康老年人跟年輕人透過阻力型運動 進步的肌力與肌肉是相近的
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- 44. 醫生，肌少症要吃什麼來補 ?? Nutrition Interventionon Muscle Health 44
- 45. Older adults needmore protein dose Nutr Metab (Lond). 2011 Oct 5;8:68. 45 more leucine
- 46. Recommended protein intakeis around 1.2g/kg/day Nutrition intervention (Protein intake) AWGS1 EWGSOP/ IWGS2 ESPEN3 ICFSR4 Protein 1.2g/kg/day EAA (~2.5 g leucine) HMB Healthy elderly 1.0g/kg/day Older Adults with illness 1.2-1.5g/kg/day Individualized Discussion with patients for the importance of adequate calorie and protein 1. Liang-Kung Chen et al. J Am Med Dir Assoc. 2020 Mar;21(3):300-307.e2.2. Cruz-Jentoft AJ, et al. Age Ageing. 2014 Nov;43(6):748-59; 3. Deutz NE, et al. Clin Nutr. 2014 Dec;33(6):929-36; 4. Dent E, et al. J Nutr Health Aging. 2018;22(10):1148-1161. Healthy elderly 1-1.2g/kg/day Sarcopenia/Frail 1.2g/kg/day Amino acid (leucine, L-carnitine), HMB 46
- 47. Protein intake recommendation Cruz-JentoftAJ, et al. Maturitas 2020;132:57-64. CKD, chronic kidney disease; GFR, glomerular filtration rate. Protein intake recommendation for adults ≥ 65 years of age Acute or chronic illness 1.2-1.5g/kg/day Severe CKD (GFR < 30 mL/min/1.73 m2) 0.6-0.8 g/kg/day The health 1.0-1.2g/kg/day 1.2 g/kg/day + 20 g protein supplement after exercise for people exercising and otherwise active* Up to 2.0 g/kg/day for those with sever illness/injury or malnutrition *Endurance exercise 30 minutes/day; Include progressive resistance training 2-3 times/week for 10–15 minutes. Protein/amino acid threshold 25-30 g per meal Containing 2.5-2.8 g leucine 47
- 48. Protein intake 15% 25% 足量蛋白質飲食重要 過多蛋白質飲食無益 PengLN, et al., Arch Gerontol Geriatr 2021;96:104436 48
- 49. Adequate protein distributionin each meal Optimal protein distribution Skewed protein distribution Maximum protein synthesis Breakfast ~30 g protein Lunch ~30 g protein Dinner ~30 g protein Breakfast ~10 g protein Lunch ~20 g protein Dinner ~60 g protein Curr Opin Clin Nutr Metab Care. 2009 Jan; 12(1): 86–90.
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- 51. Muscle growth relatedessential amino acid: Leucine Isoleucine Valine Regulate protein anabolic rate and muscle growth Branched-Chain Amino Acid (BCAA) British Journal of Nutrition (2015), 113, 25–34 Deutz NE et al. Clin Nutr. 2013;32:704-12 Peng LN, et al., Exp Gerontol Geriatr 2022;157:111644
- 52. British Journal ofNutrition (2015), 113, 25–34 The effectiveness of leucine on muscle health Muscle protein fractional synthetic rate participants with mean age >65 years Meta-analysis (9 RCTs)
- 53. 胺基酸預防肌肉流失、增加肌肉肌力 53 12 subjects(67±6 years)with glucose tolerance, taking 22g EAA+arg (7.9g leucine) for 4 months Walking speed(m/s) Muscle strength (kg) Clin Nutr. 2008 Apr;27(2):189-95.
- 54. 僅供專業醫護人員參考使用 僅供專業醫護人員參考使用 BCAA、白胺酸含量最豐富 54 使用100%乳清蛋白 Nutrients 2018;10:1937 乳清蛋白 蛋清蛋白酪蛋白 大豆蛋白 胺 基 酸 % 白胺酸 支鏈胺基酸 必需胺基酸
- 55. Liver cell cytosol (5-10%) Cholesterol Urine HMG-CoA HMG-CoA Ketone bodies Acetyl-CoA TCAcycle α-ketoisocaproic acid Leucine Liver cell mitochondria (90-95%) HMB Sarcolemma integrity2 β-hydroxy-β-methylbutyrate (HMB): metabolite of Leucine1 1. Holeček M. J Cachexia Sarcopenia Muscle 2017;8:529-41. 2. Albert FJ, et al. Nutr Hosp 2015;32:20-33. HMB, β-hydroxy-β-methylbutyrate; HMG-CoA, 3-hydroxy-3-methylglutaryl-CoA; TCA, tricarboxylic acid. β-hydroxy-β-methylbutyrate (HMB) 55
- 56. Mechanism of HMBin muscle protein 1-4 1. Smith HJ, et al. Cancer Res. 2004;64:8731-5. 2. Smith HJ, et al. Cancer Res. 2005;65:277-83. 3. Wilson GJ, et al. Nutri Metab. 2008;5:1-17. 4. Eley HL, et al. Am J Physiol Endocrinol Metab. 2007;293:E923-31. HMB, β-hydroxy-β-methylbutyrate; mTOR, mammalian target of rapamycin; NF-kB, nuclear factor kappa-light-chain-enhancer of activated B cells 56 Upregulation Protein Synthesis Downregulation Protein Degradation mTOR Casoase-8 NF-kB Turn on Ribosome Protein synthesis Inhibit Proteosome Attenuation of protein degradation
- 57. Lean body massis maintained by HMB during 10 days of bed rest in older adults (N=24) Deutz NE et al. Clin Nutr. 2013;32:704-12. 1 0.5 0 -0.5 -1.0 -1.5 -2.0 -2.5 -3.0 Change in total lean mass (kg) p=0.04 Control HMB Bed rest 10days + resistance training(8 wk) Bed rest 10days -2kg -0.66kg HMB (β-hydroxy-β-methylbutyrate)： a metabolite of Leucine β-hydroxy-β-methylbutyrate (HMB) on Muscle Health Randomized Controlled Trial
- 58. 58 HMB-ONS : Improves nutrition,physical performance and intramuscular adiposity Peng LN. et al. J Nutr Health Aging. 2021;25(6):767-773. 70 participants(mean age: 71.1 ± 3.8 years ; Female 69.3%） 12-week RCT CaHMB 3g + 1000 IU vitamin D3 vs. standard diet 70 older pre-frail older adults
- 59. 59 HMB : muscle massand muscle strength in clinical conditions Bear DE, et al. Am J Clin Nutr 2019;109:1119-32. HMB and muscle mass HMB and muscle strength 15 RCTs, 2,137 patients with a primary clinical diagnosis (e.g., COPD, cancer, malnutrition)
- 60. Taiwan Product composition 60 Ensurewith full dose HMB Ensure with half dose HMB Per serving (220 mL) % of total energy Per serving (220 mL) % of total energy Energy 330 kcal 270 kcal Protein 20 g 24.34 % 11 g 16.31 % Fat 10.6 g 28.89 % 9 g 30.02 % Carbohydrate 39.2 g 45.67 % 37 g 53.01 % CaHMB 1.5 g 0.75 g
- 61. Primary health careor community preventive services settings 61 *Include but not limit to osteoporosis, CVD, COPD, DM, CKD, HTN, immunodeficiency, etc. BMI, body mass index; CI, confidence interval; F, female; HMB, β-hydroxy-β-methylbutyrate; HR, hazard ratio; M, male; s, seconds. 1. Chen LK, et al. J Am Med Dir Assoc 2020;21:300-7.e2. 2. Kuo YH, et al. Am J Med Sci 2019;357:124-33. 3. Cruz-Jentoft AJ, et al. Age Ageing 2019;48:16-31. 4. Dirks ML, et al. Acta Physiol (Oxf) 2014;210:628- 41. 5. Lee WJ, et al. J Nutr Health Aging 2023; letter to the editor, published online. Case finding Age: ≥ 65 years1-3 Or Immobilization3,4 Or Dysphagia dysfunction1 Or Malnutrition1,3: BMI < 18.5 or > 27 kg/m2 Or With comorbidities related to muscle loss*1,3 Or Impaired mobility or subjective complaint under physician’s observation1 Appendicular skeletal muscle mass DEXA (M: <7.0 kg/m2, F: <5.4 kg/m2) Or BIA (M: <7.0 kg/m2, F: <5.7 kg/m2) Muscle strength Handgrip strength (M: < 28 kg, F: < 18 kg) Or Physical performance 5-times chair stand test: ≥ 12 s Assessment Diagnosis Possible sarcopenia Sarcopenia Recommend 1 can/day Ensure HMB (1.5 g/can HMB) Recommend 2 can/day Ensure HMB (1.5 g/can HMB) Non e General maintenance Recommend 1 can/day Ensure HMB (0.75 g/can HMB)
- 62. Acute to chronichealth care or clinical research settings 62 F, female; HMB, β-hydroxy-β-methylbutyrate; M, male. Chen LK, et al. J Am Med Dir Assoc 2020;21:300-7.e2. Case finding Age: ≥ 65 years Or Presence of any of the following clinical conditions*: • Functional decline or limitation; unintentional weight loss; depressive mood; cognitive impairment; repeated falls; malnutrition • Chronic condition (heart failure, chronic obstructive pulmonary disease, diabetes mellitus, chronic kidney disease, etc) Muscle strength Handgrip strength (M: < 28 kg, F: < 18 kg) Assessment Possible sarcopenia Recommend 1 can/day Ensure HMB (1.5 g/can HMB) Non e Medical quality improvement Recommend 1 can/day Ensure HMB (0.75 g/can HMB) Appendicular skeletal muscle mass DEXA (M: <7.0 kg/m2, F: <5.4 kg/m2) Or BIA (M: <7.0 kg/m2, F: <5.7 kg/m2) Diagnosis Sarcopenia Recommend 2 can/day Ensure HMB (1.5 g/can HMB) *Nutritional intervention can also be conducted based on HCP’s clinical judgement, such as albumin < 3.5 g/dL etc.
- 63. Vitamin D可以預防肌少症的發生 63 • 追踪96個腦中風後偏癱的老年女性持續兩年 •其中48位每天補充vitamin D2 1000 IU, 另外48位補充安慰劑 • 結果： 1. 補充vit D的老年人在兩年中跌倒的人數和次數明顯下降 2. 在顯微鏡下，補充vit D的老年人的type II fiber明顯增加，而補充 安慰劑的老年人的type II fiber更萎縮 Cerebrovasc Dis. 2005;20:187–192.
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