悪液質に対する運動仮説モデルEACH

悪液質に対する運動仮説モデルEACHの論文を紹介します。

Claudio L. Battaglini, Anthony C. Hackney, and Matthew L. Goodwin. Cancer Cachexia: Muscle Physiology and Exercise Training. Cancers 2012, 4(4), 1247-1251; doi:10.3390/cancers4041247

下記のHPから全文PDFで入手できます。

http://www.mdpi.com/2072-6694/4/4/1247

EACHモデルを図に示します。悪液質に対する運動療法は、抗炎症性サイトカインの増加、アンドロゲンの増加、炎症性サイトカインの減少によって、筋蛋白質の合成増加・分解減少を期待できるという仮説モデルです。いくつかの研究で検証されていますが、今後さらなる研究での検証が必要です。

日本ではまず前悪液質や悪液質を早期に発見、診断する体制作りが必要だと考えます。不応性悪液質になってから診断しても、このモデルのような運動療法の効果を期待することは困難です。「悪液質＝ターミナル」という過去の考え方を早くアップデートしたいですね。そして悪液質のリハ・運動療法は、重要な研究テーマです。

Abstract:
Cachexia in cancer patients is a condition marked by severe tissue wasting and a myriad of quality of life and health consequences. Cachexia is also directly linked to the issues of morbidity and survivability in cancer patients. Therapeutic means of mitigating cachexia and its effects are thus critical in cancer patient treatment. We present a discussion on the use of physical exercise activities in the context of such treatment as a means to disruption the tissue wasting effects (i.e., muscle tissue losses via anorexigenic pro-inflammatory cytokines) of cachexia. In addition we propose a theoretical model (Exercise Anti-Cachectic Hypothetical—“EACH” model) as to how exercise training may promote a disruption in the cycle of events leading to advancing cachexia and in turn promote an enhanced functionality and thus improved quality of life in cancer patients.

頭頚部がんの筋トレ＋蛋白・クレアチン

放射線療法で加療された頭頚部がん患者に対する筋トレ＋蛋白・クレアチンの効果をみたRCTを紹介します。がんのリハ栄養では重要な論文と考えます。

Simon Lønbro, et al. Feasibility and efficacy of progressive resistance training and dietary supplements in radiotherapy treated head and neck cancer patients – the DAHANCA 25A study. Acta Oncologica, 2012, DOI: 10.3109/0284186X.2012.741325

リサーチクエスチョンは以下の通りです。

P：頭頚部がん患者に
I：12週間の筋トレ＋蛋白・クレアチンを投与すると
C：12週間の筋トレのみと比較して
O：除脂肪量（一次アウトカム）、筋力、身体機能が改善する
D：ランダム化比較試験

筋トレは最初の指導後は自主トレが中心で、12週間で合計30回（週に2.5回）行いました。筋トレの内容はleg press, knee extension,hamstring curls, chest press, sit ups, back extensions and lateral pull downです。全例PSが0か1ですので、このような筋トレが可能です。

筋トレと近いタイミング（直後かと思われます）で、介入群は蛋白パウダー30gとクレアチン5g、対照群はマルトデキストリンを摂取します。

結果ですが、介入群は14人、対照群は7人が12週間の介入を完了しました（全体で70％しか完了できていないことが大きな問題です）。

介入群で除脂肪量は前後比較で有意に増加（2.6 ± 2.2 kg）し、対照群では増加傾向でした(1.3 ± 1.1 kg, p = 0.07)。 ただし、両群間の比較では統計学的有意差はありませんでした。筋力と身体機能も両群とも前後比較で有意に改善しましたが、両群間の比較では統計学的有意差はありませんでした。

以上より、放射線療法で加療された頭頚部がん患者に対する筋トレは有効という結論です。ただ、介入群で2.6kg増、対照群で1.3kg増ですので、臨床的には有意差があると考えます。脱落率が大きいために統計学的有意差が出なかったので、頭頚部がんの筋トレ直後の蛋白・クレアチン投与は有効と私は判断します。

がんのリハ栄養で、筋トレ直後の蛋白・クレアチン投与に効果があったという報告は、私はあまり聞いたことがありません。脱落率が大きかったことが残念ですが、筋トレを実施できるようながん患者には、筋トレ直後の蛋白・クレアチン投与を検討してもよいと考えます。

Abstract

Background. Patients with head and neck squamous cell carcinoma (HNSCC) often lose a considerable amount of muscle mass following the disease and treatment. This is an independent mortality predictor, lowering muscle strength and functional performance. Progressive resistance training (PRT) increases muscle mass among healthy individuals and groups of cancer patients, but it has not been investigated in HNSCC patients. Furthermore, studies in healthy subjects show an additive effect of protein and creatine supplementation following PRT. Objectives. Firstly, to investigate the feasibility of 12 weeks of PRT ± protein and creatine supplementation among HNSCC patients. Secondly, to investigate group changes over time and group differences regarding lean body mass (LBM), muscle strength and functional performance following PRT ± dietary supplementation. Material and methods. Thirty patients were randomized into two groups: a PROCR group undergoing a seven-day pre-trial creatine loading protocol followed by 12 weeks of PRT with creatine and protein supplementation and a PLA group undergoing a seven-day pre-trial placebo ingestion protocol followed by an identical PRT protocol with placebo supplementation. Before the pre-trial and pre- and post-PRT evaluation of LBM, maximal isometric and isokinetic muscle strength and functional performance were performed. Results. Seventy percent of the patients completed the intervention and the PRT adherence rate was 97%. No significant group differences were found in any endpoints. From pre- to post-PRT, LBM increased significantly in the PROCR group by 2.6 ± 2.2 kg (p < 0.0001) and increased in the PLA group (1.3 ± 1.1 kg, p = 0.07). Maximal isometric and isokinetic muscle strength as well as functional performance increased significantly in both groups. Conclusion. PRT is feasible in radiotherapy treated HNSCC patients. Following PRT, lean body mass, muscle strength and functional performance increased significantly in both groups (LBM only borderline significant in PLA group) with no significant group difference in any endpoint.

脳性麻痺の食事摂取と身体組成

就学前脳性麻痺児の食事摂取と身体組成を移動能力別にみた研究を紹介します。

Jacqueline L. Walker, et al. Relationships between Dietary Intake and Body Composition according to Gross Motor Functional Ability in Preschool-Aged Children with Cerebral Palsy. Ann Nutr Metab 2012;61:349-357 (DOI: 10.1159/000342557)

対象は就学前脳性麻痺児（平均年齢2.8歳）73人（GMFCS levelsはI = 39, II = 9, III = 9, IV = 7, V = 9。ⅠとⅡを移動自立、ⅢからⅤを移動困難の2群に分類）と、健常発達児16人です。3日間の食事摂取量と身体組成を横断研究で調査しました。

結果ですが、食事摂取量と除脂肪指数にのみ有意な関連を認め、脳性麻痺児より健常発達児のほうがより強い関連でした。身体組成と移動能力には関連を認めました。移動困難で経管栄養の場合、経口摂取と比較して蛋白摂取量が有意に少なかったです。

以上より、この年代の身体組成には食事摂取よりも身体活動レベルのほうがより大きな影響を与えている可能性があるという結論です。

脳性麻痺の場合、痙直型かアテトーゼ型かによってもエネルギー消費量がかなり異なります。タイプ分類せずに一律に脳性麻痺として研究するのは、やや無理があるのかなと感じます。食事摂取と身体活動の両方とも当然、身体組成への影響が大きいかと思います。

Abstract
Background/Aims: We aimed to determine the relationships between energy intake, macronutrient intake and body composition in preschool-aged children with cerebral palsy (CP) according to gross motor functional ability in comparison with typically developing children (TDC). Methods: Seventy-three children with CP (70% male) of all functional abilities and 16 TDC (63% male) aged 2.8 ± 0.9 years participated in this study. Dietary intake was measured via a validated 3-day weighed food record. Body composition was determined via isotope dilution techniques. Results: There was a significant relationship between energy intake and fat-free mass index, which was stronger in TDC compared to children with CP. There were no significant correlations between other dietary intake and body composition variables, despite differences in body composition as ambulatory status declined. Non-ambulant, tube-fed children had significantly lower protein intakes compared to orally fed children. No other differences in macronutrient intake between children with CP and TDC were apparent. Conclusions: Results suggest that relationships between dietary intake and body composition are not evident in this population, but develop over time. Physical activity levels may have a greater impact on body composition at this age. Longitudinal research is required to examine these factors.

2型糖尿病の筋蛋白同化

2型糖尿病の筋蛋白同化のレビュー論文を紹介します。

Bassil MS, Gougeon R. Muscle protein anabolism in type 2 diabetes. Curr Opin Clin Nutr Metab Care. 2012 Nov 28. [Epub ahead of print]

2型糖尿病では筋蛋白同化の異常を認めます。加齢による筋萎縮を加速させます。これはインスリン抵抗性に関連していると思われます。一方、アミノ酸、特にBCAAの投与によってインスリン抵抗性を克服できるかもしれません。

高齢2型糖尿病患者に対するロイシン投与の先行研究では、筋肉量増加を認めませんでした。しかし、この研究ではサルコペニアではなく十分なタンパク質を摂取していたので、非定型な結果かもしれません。運動や身体活動も蛋白同化のインスリン抵抗性の克服に有効かもしれません。

糖尿病では筋障害による筋萎縮だけでなく、末梢神経障害による筋萎縮も合併しやすいです。また糖尿病性腎症で慢性腎不全となった場合、悪液質も合併することがあります。このように広義のサルコペニアの原因が多彩となるため、適切な評価と対応が求められます。

Abstract

PURPOSE OF REVIEW:

Protein anabolism is abnormal in human type 2 diabetes (T2DM). We review studies of anabolic stimuli that identify potential causes. If uncorrected, and combined with aging effects, they will compromise muscle function and mass. Knowing causes can guide studies of preventive and treatment measures.

RECENT FINDINGS:

T2DM accelerates age-related decreases in muscle mass. This could be related to insulin resistance of whole-body protein anabolism demonstrated in hyperglycemic obese men. In contrast, their protein anabolic response to hyperaminoacidemia suggested that ample amino acid administration, especially branched chain amino acids might overcome such insulin resistance. One study of chronic leucine supplementation in elderly T2DM patients did not increase muscle mass. However, they lacked sarcopenia and had adequate dietary protein intake, so may be atypical. Exercise induced similar increases in muscle protein synthesis, mass and strength in healthy and T2DM patients suggesting that physical activity might also overcome insulin resistance of protein anabolism.

SUMMARY:

Muscle protein anabolism in T2DM is resistant to the action of insulin but perhaps not to amino acid supply or exercise. Whether leucine supplementation improves muscle mass and function in persons with T2DM (especially elderly) with reduced protein intake or muscle mass needs to be determined.

肥満女性の減量・運動とサルコペニア

閉経後の過栄養～肥満女性に対する食事、運動、ビタミンDがサルコペニアに与える影響を調査した論文を紹介します。

Mason C, Xiao L, Imayama I, Duggan CR, Foster-Schubert KE, Kong A, Campbell KL, Wang CY, Villasenor A, Neuhouser ML, Alfano CM, Blackburn GL, McTiernan A. Influence of Diet, Exercise, and Serum Vitamin D on Sarcopenia in Postmenopausal Women. Med Sci Sports Exerc. 2012 Nov 27. [Epub ahead of print]

対象は439人の閉経後の過栄養～肥満女性で、12ヶ月間、食事療法群、運動療法群、食事＋運動群、対照群の4群に分けられました。食事療法は10％の体重減少を目標としました。運動療法は1日45分、週5回の中強度の有酸素運動です。

結果ですが、食事療法群では筋肉量が対照群より有意に低下しました。運動療法群では筋肉量が保たれていました。食事＋運動群では筋肉量減少を認めましたが、食事療法群よりその程度は軽く、対照群と比べて有意差はありませんでした。

以上より、減量時の有酸素運動は筋肉量減少を緩和し、サルコペニア予防となる可能性があるという結論です。

サルコペニア予防には有酸素運動よりレジスタンストレーニングのほうが効果を期待できますが、有酸素運動でも一定の効果はあるようです。食事療法だけで減量すると筋肉が減って、その後リバウンドすると脂肪で増えるので、サルコペニア肥満に一直線ですね。

Abstract

PURPOSE:

To investigate the effects of 12 months of dietary weight loss and/or aerobic exercise on lean mass and the measurements defining sarcopenia in postmenopausal women, and to examine the potential moderating effect of serum 25-hydroxyvitamin D (25(OH)D) and age.

METHODS:

439 overweight and obese postmenopausal women were randomized to: diet modification (N=118); exercise (N=117), diet+exercise (N=117), or control (N=87). The diet intervention was a group-based program with a 10% weight loss goal. The exercise intervention was 45 mins/day, 5 days/week of moderate-to-vigorous intensity aerobic activity. Total and appendicular lean mass were quantified by dual Xray absorptiometry (DXA) at baseline and 12 months. A skeletal muscle index (SMI=appendicular lean mass (kg)/m) and the prevalence of sarcopenia (SMI<5 .67=".67" calculated.="calculated." class="highlight" kg="kg" m="m" span="span" were="were">Serum
25(OH)D was assayed using a competitive chemiluminescent immunoassay.

RESULTS:

Dietary weight loss resulted in a significant decrease in lean mass, and a borderline significant decrease in appendicular lean mass and SMI compared to controls. In contrast, aerobic exercise significantly preserved appendicular lean mass and SMI. Diet + exercise attenuated the loss of appendicular lean mass and SMI compared to diet alone, and did not result in significant loss of total- or appendicular lean mass compared to controls. Neither serum 25(OH)D nor age were significant moderators of the intervention effects.

CONCLUSIONS:

Aerobic exercise added to dietary weight loss can attenuate the loss of appendicular lean mass during weight loss, and may be effective for the prevention and treatment of sarcopenia among overweight and obese postmenopausal women.

サルコペニア肥満と変形性膝関節症

サルコペニア肥満では変形性膝関節症が多いという横断研究です。

Lee S, Kim TN, Kim SH. Sarcopenic obesity is more closely associated with knee osteoarthritis than is nonsarcopenic obesity: A cross-sectional study. Arthritis Rheum. 2012 Dec;64(12):3947-54. doi: 10.1002/art.37696.

サルコペニアはDEXAで筋肉量が若年の2SD以下の場合としています。サルコペニアでない肥満のカットオフ値は、BMI27.5以上としています。

結果ですが、サルコペニア肥満では、サルコペニアでない肥満の場合より、同じ体重であっても変形性膝関節症の有病割合が高かったです。サルコペニアで肥満でない場合には、変形性膝関節症のリスクではありませんでした。

サルコペニア、変形性膝関節症ともロコモティブシンドロームの原因の1つですが、サルコペニア肥満の場合には変形性膝関節症を合併しやすくなるため、よりロコモの可能性も高くなるのだと思います。ロコモでは低栄養も問題ですが、サルコペニア肥満も問題ですね。

Abstract

OBJECTIVE:

Sarcopenic obesity is a body composition category in which obesity is accompanied by low skeletal muscle mass, offsetting the increase in body weight caused by increased adipose tissue. The purpose of this study was to analyze the association between knee osteoarthritis (OA) and 4 different categories of body composition: normal, sarcopenic nonobesity, nonsarcopenic obesity, and sarcopenic obesity.

METHODS:

This was a cross-sectional study using the data from 2,893 participants in the Fifth Korean National Health and Nutrition Examination Survey. Radiographic knee OA was defined as a Kellgren/Lawrence grade of ≥2. Appendicular skeletal muscle mass (ASM) and whole-body fat mass were measured using dual x-ray absorptiometry. Sarcopenia was defined as a skeletal muscle mass index (ASM/body weight [%]) below -2SD of the value in sex-matched young reference groups. Nonsarcopenic obesity was defined as a body mass index (BMI) ≥27.5 kg/m(2) .

RESULTS:

The prevalence of each body composition category was as follows: 83.5% normal, 4.3% sarcopenic nonobesity, 9.2% nonsarcopenic obesity, and 3.0% sarcopenic obesity. Compared with nonsarcopenic obesity participants, participants with sarcopenic obesity were significantly older, had lower ASM, higher whole-body fat mass, and higher waist circumference. However, there was no significant difference in body weight or BMI. In multivariate analysis, sarcopenic obesity was more closely associated with radiographic knee OA (OR 3.51 [95% confidence interval (95% CI) 2.15-5.75]) than was nonsarcopenic obesity (OR 2.38 [95% CI 1.80-3.15]). Sarcopenic nonobesity showed no significant association with knee OA.

CONCLUSION:

Sarcopenic obesity was more closely associated with knee OA than was nonsarcopenic obesity, although both groups had equivalent body weight. This finding supports the importance of the systemic metabolic effect of obesity in knee OA.

透析患者のエネルギーバランス

透析患者のエネルギーバランスを7日間調査した論文を紹介します。

Bovio G, Montagna G, Brazzo S, Piazza V, Segagni S, Cena H. Energy balance in haemodialysis and peritoneal dialysis patients assessed by a 7-day weighed food diary and a portable armband device. J Hum Nutr Diet. 2012 Nov 28. doi: 10.1111/j.1365-277x.2012.01291.x. [Epub ahead of print]

対象は人工透析患者、腹膜透析患者8人ずつで、研究デザインは横断研究です。
結果ですが、両群ともエネルギーバランスはマイナス（1日当たり300kcal台）でした。CRPと1日エネルギー消費量、除脂肪体重に逆相関を認めました。

以上より、透析患者ではエネルギーバランスがマイナスで低栄養のリスクがあるという結論です。目新しいことはあまりありませんが、それでも論文にすることに意義があると感じました。このくらいの研究なら、臨床に従事している日本の医療人でも十分できますよね。

Abstract

BACKGROUND:

Energy balance (EB) is important when assessing nutritional status. EB has never been assessed in haemodialysis (HD) and peritoneal dialysis (PD) patients. The present study aimed to assess weekly EB in these patients.

METHODS:

This clinical cross-sectional study was conducted for 7 days in eight HD and eight PD patients. Nutritional status was assessed by anthropometry, bioelectrical impedance analysis and biochemical markers. Energy intake (EI per day) and total energy expenditure (TEE per day) were determined by a 7-day weighed food diary and a portable armband device, respectively.

RESULTS:

No significant differences in age, body mass index, fat free mass (FFM), parathyroid hormone were found between the two groups. EB was calculated by subtracting TEE per day from EI per day. EB was negative in HD {-1347 (1276) kJ day(-1) [-322 (305) kcal day(-1) ]}, as well as in PD patients {-427 (5338) kJ day(-1) [-102 (395) kcal day(-1) ]}. TEE per day was positively correlated with EI per day, prealbumin, FFM. EI per day was positively correlated with prealbumin. C-reactive protein was negatively correlated with TEE and FFM (P < 0.05). EB showed a positive correlation with EI per day (P = 0.012) and a negative trend with TEE.

CONCLUSIONS:

HD and PD patients have a negative EB and are at risk of malnutrition. Inflammatory status determines a lower EI per day and a reduction in TEE per day. The most important parameter in determining EB in HD and PD patients is EI per day. This topic deserves further investigation to better understand the mechanisms of impaired EB with respect to preserving patients' nutritional status.