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"[Latar belakang: Gagal jantung adalah penyebab utama kematian pada thalassemia akibat penumpukan besi dari transfusi darah. Ekokardiografi sering digunakan untuk evaluasi fungsi jantung, namun interpretasi hasilnya sangat bergantung dari operator. Uji berjalan 6 menit adalah metode sederhana yang terbukti mempunyai reliabilitas baik untuk menilai kapasitas fungsional kardiorespirasi sehingga dapat menjadi alternatif penilaian fungsi jantung anak thalassemia.Tujuan: Mendapatkan uji berjalan 6 menit sebagai metode sederhana untuk mengukur fungsi jantung anak thalassemia.Metode: Penelitian kasus kontrol pada subjek thalassemia dan kontrol berusia 11-18 tahun yang dipilih secara consecutive sampling. Subjek thalassemia mempunyai rerata feritin serum >2500 ng/mL dalam 6 bulan terakhir. Subjek kontrol dalam kondisi sehat dan tidak pernah menjalani transfusi darah. Uji berjalan 6 menit dilakukan pada kedua subjek, sedangkan ekokardiografi konvensional (EK) dan tissue Doppler (ETD) hanya dilakukan pada subjek thalassemia oleh seorang konsultan kardiologi anak. Data sekunder lain pada subjek thalassemia diambil dari rekam medis yaitu rerata hemoglobin pra-transfusi dalam 1 tahun terakhir, feritin serum dan saturasi transferin dalam 6 bulan terakhir.Hasil: Sebanyak 40 subjek thalassemia dan 109 kontrol berpartisipasi dalam penelitian ini. Median usia subjek thalassemia 13,4 (11-17,9) tahun dan kontrol 14,2 (11,3-17,9) tahun. Rerata hemoglobin pra-transfusi 7,6±0,6 g/dL. Median feritin serum 4246,5 (2506-10749,7) ng/mL dan saturasi transferin 100 (50-100) %. Setelah dilakukan matching usia dan jenis kelamin, jarak tempuh uji berjalan 6 menit pada subjek thalassemia lebih pendek daripada kontrol (465,1±74,2 vs 671±94,2, p<0,001). Parameter fungsi sistolik dan diastolik jantung dari EK dalam batas normal, tetapi ETD menunjukkan 45% subjek thalassemia mengalami gangguan fungsi diastolik (rasio E/E’ >8). Tidak ada faktor yang berkorelasi dengan jarak tempuh pada subjek thalassemia, sedangkan tinggi badan berkorelasi dengan jarak tempuh pada kontrol berdasarkan analisis bivariat.Kesimpulan: Jarak tempuh antara subjek thalassemia lebih rendah daripada kontrol. Peran ETD lebih baik daripada EK dalam mengevaluasi fungsi jantung. Uji berjalan 6 menit dapat digunakan sebagai skrining fungsi jantung pada anak thalassemia.;Background: Heart failure is leading cause of mortality in thalassemia due to transfusion-induced iron overload. Evaluation of cardiac function is routinely performed with echocardiography. However, its interpretation depends on operator. The six minute walk test is a simple and reliable method to assess cardiorespiratory performance, therefore, it is suggested to be an alternative in evaluating cardiac function in thalassemia.Aim: To obtain six minute walk test as a simple method in order to evaluating cardiac function in thalassemia.Methods: This case control study was performed in thalassemia subjects (cases) and controls aged 11-18 year old which were selected with consecutive sampling. Cases should have mean serum ferritin level >2500 ng/mL in last 6 months. Controls must be in healthy condition and have never had blood transfusion. Both cases and controls performed six minute walk test, while echocardiography (conventional and tissue Doppler) was only done in cases by a pediatric cardiologist. Other secondary data collected from medical records in cases were mean of pre-transfusion hemoglobin in last 1 year, serum ferritin and transferin saturation in last 6 months.Results: There were 40 cases and 109 controls involved in this study with median age were 13.4 (11-17.9) and 14.2 (11.3-17.9), respectively. The mean of pre-transfusion hemoglobin was 7,6±0,6 g/dL. The median serum ferritin was 4246.5 (2506-10749.7) ng/mL and transferin saturation 100 (50-100) %. After sex and age matching, the six minute walk distance was lower in cases than controls (465.1±74.2 vs 671±94.2, p<0.001). Conventional echocardiography did not find any systolic and diastolic dysfunction in cases. However, tissue Doppler echocardiography found 18 (45%) subjects with E/E’ ratio >8, which were categorized as diastolic dysfunction. There were no factors correlated to six minute walk distance in cases, while body height was correlated to six minute walk distance in controls based on bivariat analysis.Conclusion: The distance of six minute walk test in thalassemia subjects was shorter than controls. Tissue Dopper echocardiography is better than conventional in order to evaluating cardiac function. The six minute walk test can be used for screening cardiac function in thalassemia.;Background: Heart failure is leading cause of mortality in thalassemia due to transfusion-induced iron overload. Evaluation of cardiac function is routinely performed with echocardiography. However, its interpretation depends on operator. The six minute walk test is a simple and reliable method to assess cardiorespiratory performance, therefore, it is suggested to be an alternative in evaluating cardiac function in thalassemia.Aim: To obtain six minute walk test as a simple method in order to evaluating cardiac function in thalassemia.Methods: This case control study was performed in thalassemia subjects (cases) and controls aged 11-18 year old which were selected with consecutive sampling. Cases should have mean serum ferritin level >2500 ng/mL in last 6 months. Controls must be in healthy condition and have never had blood transfusion. Both cases and controls performed six minute walk test, while echocardiography (conventional and tissue Doppler) was only done in cases by a pediatric cardiologist. Other secondary data collected from medical records in cases were mean of pre-transfusion hemoglobin in last 1 year, serum ferritin and transferin saturation in last 6 months.Results: There were 40 cases and 109 controls involved in this study with median age were 13.4 (11-17.9) and 14.2 (11.3-17.9), respectively. The mean of pre-transfusion hemoglobin was 7,6±0,6 g/dL. The median serum ferritin was 4246.5 (2506-10749.7) ng/mL and transferin saturation 100 (50-100) %. After sex and age matching, the six minute walk distance was lower in cases than controls (465.1±74.2 vs 671±94.2, p<0.001). Conventional echocardiography did not find any systolic and diastolic dysfunction in cases. However, tissue Doppler echocardiography found 18 (45%) subjects with E/E’ ratio >8, which were categorized as diastolic dysfunction. There were no factors correlated to six minute walk distance in cases, while body height was correlated to six minute walk distance in controls based on bivariat analysis.Conclusion: The distance of six minute walk test in thalassemia subjects was shorter than controls. Tissue Dopper echocardiography is better than conventional in order to evaluating cardiac function. The six minute walk test can be used for screening cardiac function in thalassemia., Background: Heart failure is leading cause of mortality in thalassemia due to transfusion-induced iron overload. Evaluation of cardiac function is routinely performed with echocardiography. However, its interpretation depends on operator. The six minute walk test is a simple and reliable method to assess cardiorespiratory performance, therefore, it is suggested to be an alternative in evaluating cardiac function in thalassemia.Aim: To obtain six minute walk test as a simple method in order to evaluating cardiac function in thalassemia.Methods: This case control study was performed in thalassemia subjects (cases) and controls aged 11-18 year old which were selected with consecutive sampling. Cases should have mean serum ferritin level >2500 ng/mL in last 6 months. Controls must be in healthy condition and have never had blood transfusion. Both cases and controls performed six minute walk test, while echocardiography (conventional and tissue Doppler) was only done in cases by a pediatric cardiologist. Other secondary data collected from medical records in cases were mean of pre-transfusion hemoglobin in last 1 year, serum ferritin and transferin saturation in last 6 months.Results: There were 40 cases and 109 controls involved in this study with median age were 13.4 (11-17.9) and 14.2 (11.3-17.9), respectively. The mean of pre-transfusion hemoglobin was 7,6±0,6 g/dL. The median serum ferritin was 4246.5 (2506-10749.7) ng/mL and transferin saturation 100 (50-100) %. After sex and age matching, the six minute walk distance was lower in cases than controls (465.1±74.2 vs 671±94.2, p<0.001). Conventional echocardiography did not find any systolic and diastolic dysfunction in cases. However, tissue Doppler echocardiography found 18 (45%) subjects with E/E’ ratio >8, which were categorized as diastolic dysfunction. There were no factors correlated to six minute walk distance in cases, while body height was correlated to six minute walk distance in controls based on bivariat analysis.Conclusion: The distance of six minute walk test in thalassemia subjects was shorter than controls. Tissue Dopper echocardiography is better than conventional in order to evaluating cardiac function. The six minute walk test can be used for screening cardiac function in thalassemia.]"

"ABSTRAKTerapi metformin berpotensi untuk memperbaiki sindrom frailty dengan memodifikasi resistensi insulin, inflamasi, dan konsentrasi miostatin.Penelitian ini bertujuan untuk mengkaji peran metformin terhadap kekuatan genggam tangan, kecepatan berjalan, konsentrasi miostatin serum, dan kualitas hidup terkait kesehatan pada pasien usia lanjut dengan pre-frail.Uji klinis acak tersamar ganda dilakukan pada pasien rawat jalan berusia 60 tahun dengan status pre-frail yang direkrut secara konsekutif Maret 2015 ndash;Juni 2016 di RSCM. Pasien dieksklusi bila menyandang diabetes melitus, skor Geriatric Depression Scale ge; 10, skor Abbreviated Mental Test < 8, fase akut penyakit, dan kontraindikasi terhadap metformin. Evaluasi luaran penelitian dilakukan sebelum dan pasca-intervensi selama 16 minggu.Randomisasi terhadap 120 subjek menempatkan 60 subjek untuk tiap kelompok perlakuan. Sebanyak 43 subjek kelompok metformin 3 x 500 mg dan 48 subjek kelompok plasebo menyelesaikan penelitian. Terdapat peningkatan kecepatan berjalan yang bermakna dengan rerata sebesar 0,39 0,77 detik atau 0,13 0,24 meter/detik pada kelompok metformin dan tetap bermakna setelah dilakukan penyesuaian terhadap faktor prognostik penting yang tidak setara p = 0,024 . Pada analisis ITT ada tidaknya peningkatan kecepatan berjalan > 0,1 meter/detik didapatkan ARR 8,3 IK95 -7,9 ndash;24 , dengan NNT sebesar 12. Tidak terdapat perbedaan bermakna kekuatan genggam tangan, konsentrasi miostatin serum, dan kualitas hidup terkait kesehatan antara kedua kelompok perlakuan. Konsentrasi miostatin serum berkorelasi negatif lemah r = -0,247; p = 0,018 dengan kecepatan berjalan, namun tidak berkorelasi dengan kekuatan genggam tangan. Skor indeks EQ-5D berkorelasi positif sedang dengan kecepatan berjalan r = 0,566; p = 0,000 dan berkorelasi positif lemah dengan kekuatan genggam tangan r = 0,355; p = 0,001.Sebagai simpulan, pemberian metformin 3 x 500 mg selama 16 minggu secara statistik dan klinis bermakna dalam meningkatkan kecepatan berjalan sebagai salah satu dimensi kualitas hidup terkait kesehatan, namun belum dapat meningkatkan skor indeks EQ-5D, tidak meningkatkan kekuatan genggam tangan, dan belum menurunkan konsentrasi miostatin serum.Kata kunci. kecepatan berjalan, kekuatan genggam tangan, kualitas hidup terkait kesehatan, metformin, miostatin, pre-frail, usia lanjut.

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ABSTRACT

Metformin is considered to have potential effects to improve frailty syndrome by modifying insulin resistance, inflammation, and myostatin serum level.

This study aimed at investigating the effect of metformin on handgrip strength, gait speed, myostatin serum level, and health related quality of life HR QoL in pre frail elderly.

A double blind randomized controlled trial was conducted on elderly outpatients aged 60 years and older with pre frail status consecutively recruited from March 2015 to June 2016 at Cipto Mangunkusumo Hospital. Patients with history of diabetes mellitus, Geriatric Depression Scale score ge 10, Abbreviated Mental Test score 8, acute phase of diseases, and contraindication s to metformin were excluded. The measurement of study outcomes was conducted at baseline and after 16 weeks of intervention.

One hundred twenty subjects were randomized and equally assigned into metformin 3 x 500 mg or placebo group. There were 43 subjects in metformin group and 48 subjects in placebo group completed the intervention. The mean gait speed in metformin group significantly improved by 0.39 0.77 second or 0.13 0.24 meter second, even after adjusted for importance prognostic factors p 0,024 . Intention to treat analysis on the presence or absence of increased gait speed 0.1 meter second showed ARR 8.3 95 CI 7.9 ndash 24 , with NNT of 12. There were no significant differences on handgrip strength, myostatin serum level, and HR QoL between the two intervention groups. Myostatin serum level had weak negative correlation with gait speed r 0.247 p 0.018 , but did not correlate with handgrip strength. EQ 5D index had moderate positive correlation with gait speed r 0.566 p 0.000 and weak positive correlation with handgrip strength r 0.355 p 0.001.

In conclusion, metformin 3 x 500 mg for 16 weeks significantly improved gait speed as one of the HR QoL dimensions, but not significantly improved the EQ 5D index score and handgrip strength nor decreased myostatin serum level.

Keywords. gait speed, handgrip strength, health related quality of life, metformin, myostatin, pre frail, elderly."