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Latar Belakang: Diabetes melitus (DM) tipe 2 adalah suatu penyakit metabolik yang kompleks dan kronis yang ditandai dengan gangguan angiogenesis. Inflamasi kronis derajat ringan dan stres oksidatif yang meningkat pada DM tipe 2 diketahui dapat menyebabkan gangguan fungsi biologis pada sel progenitor/sel punca vaskular, salah satunya adalah adipose-derived mesenchymal stem cell (ADSC). Sejumlah penelitian menunjukkan potensi vaskulogenik ADSC dan perannya pada regenerasi jaringan. Hingga saat ini aplikasi sel punca autologus pada penderita DM untuk menginisiasi vaskularisasi masih mengalami kendala. Platelet-rich plasma (PRP) diketahui kaya akan berbagai faktor pertumbuhan, termasuk VEGF, yang penting untuk proses angiogenesis.

Tujuan: Penelitian ini bertujuan untuk menguji dan menganalisis efek pemberian PRP PMI terhadap proliferasi (jumlah sel stromal, nilai population doubling time (PDT), dan persentase sel hidup), diferensiasi (pembentukan koloni, ekspresi CD73, CD90, CD105, dan tiga lini diferensiasi), ekspresi mRNA VEGF dan VEGFR2, dan potensi angiogenik ADSC DM in vitro (sekresi VEGF dan pembentukan tubular kapiler).

Metode: Terlebih dahulu, konsentrasi trombosit per µL dan kadar VEGF per 1x10³ trombosit pecah yang terkandung dalam PRP Palang Merah Indonesia (PMI) dibandingkan dengan PRP DM dan non-DM. Lalu, stromal vascular fraction (SVF) diisolasi dari jaringan lemak menggunakan metode enzimatik, dan SVF penderita DM tipe 2 (n= 15) dan non-DM (n= 10)  dikultur dalam medium kontrol hingga didapat ADSC pasase 1−3 (P1−P3). Proliferasi, diferensiasi, ekspresi mRNA VEGF dan VEGFR2, serta potensi angiogenik ADSC DM dan non-DM diukur dan dibandingkan. ADSC DM P3 kemudian dikultur dalam medium PRP PMI 5%, 10%, 15%, dan 20%, lalu proliferasi, diferensiasi, ekspresi mRNA VEGF dan VEGFR2 diukur dan dibandingkan dengan kontrol (FBS) untuk mendapatkan konsentrasi PRP optimum. ADSC DM P3 yang diprekondisikan dengan PRP optimum, dengan atau tanpa anti-VEGF (bevacizumab) 100 ng/mL, dan ADSC DM P3 kontrol dikultur, lalu sekresi VEGF dan pembentukan tubular kapiler pada Matrigel^® diukur.

Hasil: Pada penelitian ini tidak ditemukan perbedaan bermakna antara konsentrasi trombosit per µL PRP DM, non-DM, dan PMI (p= 0,22). Namun, PRP non-DM memiliki kadar VEGF per 1000 trombosit pecah lebih rendah bermakna (0,20 (0,04−0,35) fg) dibandingkan PRP DM (0,69 (0,21−1,17) fg), p= 0,03) dan PMI (1,84 (1,38−2,10) p= 0,01), dan tidak ada perbedaan bermakna antara PRP DM dan PRP PMI (p= 0,06). Jumlah sel stromal per gram lemak dan jumlah koloni sel stromal DM lebih rendah dari non-DM (86,35 (52,48−106,76) x 10⁶ vs 158,93 (101,59−185,94) x 10⁶, p= 0,01, dan 94 ± 14 koloni vs 31 ± 32 koloni, p= 0,004). Tidak terdapat perbedaan bermakna antara DM dan non-DM pada persentase sel stromal hidup (p= 0,24), ekspresi CD73 (p= 0,21), CD90 (p= 0,90), adipogenesis, kondrogenesis, osteogenesis, PDT P2 (p= 0,27), PDT P3 (p= 0,21), dan persentase sel hidup ADSC P2 (p= 0,07), sedangkan ekspresi CD105 (64,41 (51,20−73,38)% vs 91,40 (82,62−95,47)%, p< 0,001) ADSC DM P1 dan persentase sel hidup (82,70 ± 8,07% vs 91,15 ± 3,77%, p= 0,04) ADSC DM P3 lebih rendah bermakna dibandingkan ADSC non-DM. Tidak ada penurunan yang bermakna pada ekspresi relatif mRNA VEGF (0,64 (0,30−1,08), p= 0,86) dan VEGFR2 DM (0,64 ± 0,56, p= 0,49) jika dibandingkan dengan ADSC non-DM. Rerata kadar VEGF dalam conditioned medium (CM) yang disekresikan oleh 1x10³ ADSC DM dan non-DM secara berturut-turut sebesar 0,74 pg/mL dan 0,62 pg/mL. ADSC DM yang diberi PRP optimum, yaitu 15% memiliki nilai PDT yang lebih rendah (2,33 ± 0,56 hari vs 5,04 ± 1,26 hari, p= 0,01) dan persentase sel hidup (95,53 ± 1,60% vs 78,95 ± 10,13%, p=0,01) yang lebih tinggi bermakna dibandingkan dengan kontrol. Terjadi peningkatan ekspresi CD105, mRNA VEGF, dan VEGFR2 ADSC DM yang diberi PRP 15% (secara berturut-turut 1,81 ± 0,73, p= 0,01; 5,27 ± 5,69, p= 0,23; dan 9,01 ± 11,59, p= 0,06) relatif terhadap kontrol. ADSC DM yang diberi PRP 15% dan ADSC DM kontrol secara berturut-turut mensekresikan VEGF rerata sebanyak 0,57 pg/mL dan 1,67 pg/mL per 1x10³ sel hidup. Jumlah tubular kapiler in vitro ADSC DM yang diberi PRP meningkat pada jam ke-24 jika dibandingkan dengan kontrol dan tidak berbeda bermakna dengan ADSC non-DM, namun membutuhkan waktu lebih panjang, serta tidak berbeda bermakna dengan ADSC DM yang diberi PRP dan anti-VEGF (p=0,78).

Kesimpulan: ADSC DM terbukti mengalami kerusakan selular yang dicirikan dengan penurunan proliferasi, diferensiasi, ekspresi mRNA VEGF dan VEGFR2, serta potensi angiogeniknya. Pemberian PRP 15% (VEGF 98,00 pg/mL) dapat memperbaiki kerusakan tersebut melalui efek sinergis yang dihasilkan oleh VEGF dan faktor pertumbuhan lainnya yang terdapat dalam PRP.

 

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Background: Type II diabetes mellitus (DM type 2) is a chronic and complex metabolic disease identified by impaired angiogenesis. Low grade chronic inflammation and increasing oxidative stress in DM type 2 decrease the biological functions of progenitor/stem cells, including adipose-derived stem cells (ADSC).  ADSC plays significant roles in angiogenesis and tissue regeneration. Some studies have shown the vasculogenic potency of ADSC and its role in tissue regeneration. To date, autologous cell application in DM patients to initiate vascularization is hindered. Platelet-rich plasma (PRP) is widely known to contain generous amount of growth factors including VEGF with significant role in angiogenesis.

Objective: This study aimed to investigate and analyze the effect of PRP preconditioning to the proliferation (stromal cell number, population doubling time (PDT) and percentage of viable cells), differentiation (colony formation, CD73, CD90, CD105 expressions, three lineage of differentiation), expression of mRNA VEGF and VEGFR2, as well as in vitro angiogenic potency of ADSC DM (VEGF secretion and capillary tube formation).

Methods: Initially, platelet concentration per µL and VEGF per 1x10³ lysed platelet contained in Palang Merah Indonesia (PMI) PRP was compared to DM and non-DM PRP. Subsequently, stromal vascular fraction (SVF) from 15 DM and 10 non-DM donors was enzymatically isolated from adipose tissue, and cultured in control media to generate passage 1−3 (P1−P3) ADSC. Proliferation, differentiation, mRNA VEGF and VEGFR2 expression, as well as angiogenic potency of DM ADSC in vitro were measured and compared to non-DM control. P3 DM ADSC was then cultured in media contained 5%, 10%, 15%, and 20% PMI PRP, and proliferation, differentiation, mRNA VEGF and VEGFR2 expression were measured and compared to FBS control to determine optimum PMI PRP concentration. P3 DM ADSC preconditioned with optimum PMI PRP, with or without anti-VEGF (bevacizumab) 100 ng/mL, and control DM ADSC were cultured, and VEGF secretion was measured, as well as capillary tube formation on Matrigel^®.

Results: In this study no significant differences were observed between platelet concentration per µL DM, non-DM, and PMI PRP (p= 0.22). However, non-DM PRP contained significantly lower VEGF per 1000 lysed platelets (0.20 (0.04−0.35) fg) compared to DM (0.69 (0.21−1.17) fg, p= 0.03) and PMI PRP (1.84 (1.38−2.10), p= 0.01), with no significant difference between DM and PMI PRP (p=0.06). The number of viable stromal cells per gram adipose tissue and collonies generated from DM SVF were significantly lower than non-DM (86.35 (52.48−106.76) x 10⁶ vs 158.93 (101.59−185.94) x 10⁶, p= 0.01 and 94 ± 14 collonies vs 31 ± 32 collonies, p= 0.004). Non-significant differences were also observed in the percentage of viable stromal cells (p= 0.24), expression of CD73 (p= 0.21), CD90 (p= 0.90), adipogenesis, chondrogenesis, osteogenesis, P2 and P3 PDT (p= 0.27 and 0.21, respectively), and the percentage of viable P2 ADSC (p= 0.07), but the expression of CD105 of P1 DM ADSC (64.41 (51.20−73.38)% vs 91.40 (82.62−95.47)%, p< 0.001) and the percentage of viable P3 ADSC (82.70 ± 8.07% vs 91.15 ± 3.77%, p= 0.04) were significantly lower than non-DM ADSC. The reduction of mRNA VEGF and VEGFR2 relative expression of P3 DM ADSC (0.64 (0.30−1.08) p= 0.86 and 0.64 ± 0.56, p= 0.49, respectively) were unsignificant compared to non-DM ADSC. Mean of VEGF level normalized to 1x10³ viable cells in the conditioned medium (CM) of DM and non-DM ADSC were 0.74 pg/mL and 0.62 pg/mL, respectively. Optimum 15% PRP-preconditioned DM ADSC had significantly lower PDT value (2.33 ± 0.56 days vs 5.04 ± 1.26 days, p=0.01) and higher percentage of viable cells compared to control (95.53 ± 1.60% vs 78.95 ± 10.13%, p=0.01). The increase of relative expression of CD105, mRNA VEGF and VEGFR2 (1.81 ± 0.73, p= 0.01; 5.27 ± 5.69, p= 0.23; and 9.01 ± 11.59, p= 0.06, respectively) were unsignificant in DM ADSC compared to non-DM. Optimum 15% PRP-preconditioned DM ADSC and control secreted VEGF in CM as much as 0.57 pg/mL and 1.67 pg/mL per 1x10³ viable cells in average. PRP-preconditioning improved the capillary tube formation in DM ADSC, but the process was longer compared to control, and unsignificant to non-DM ADSC and PRP-preconditioned DM ADSC with anti-VEGF (p=0.78).

Conclusions: Cellular damage in DM ADSC was idientified by a reduction of proliferation, differentiation. mRNA VEGF and VEGFR2 expression, and angiogenic potency. Preconditioning DM ADSC with 15% PRP (VEGF 98.00 pg/mL) improved the cellular damage with synergitic effect of VEGF and other growth factors contained in PRP.

 

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"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."

"ABSTRAKProgram latihan untuk penatalaksanaan Diabetes Melitus DM tipe 2 harus dipastikan aspek keamanannya, selain juga efektif dan bermanfaat. Melalui penelitian dua tahap dilakukan perancangan latihan fisik yang dievaluasi dengan randomized controlled trial RCT .Program latihan 12 minggu mengombinasikan high intensity interval training HIIT dan latihan beban tiga dan dua kali per minggu dengan peningkatan intensitas bertahap. HIIT terdiri atas perbandingan 1 : 4 menit high intensity exercise HIE dan low intensity exercise LIE . Latihan beban terdiri atas sembilan latihan untuk batang tubuh, ekstremitas atas, dan bawah. RCT diikuti 42 penyandang DM tipe 2 berusia 35 ndash;64 tahun, yang dialokasikan menjadi kelompok eksperimen dengan latihan sesuai rancangan dan kelompok kontrol dengan continuous cardiorespiratory training. Pemeriksaan tingkat kebugaran VO2max , kontrol glikemik HbA1c , dan stres oksidatif MDA dan SOD dilakukan di awal dan akhir program.Pasca latihan didapatkan nilai rerata VO2max kelompok eksperimen 38,13 5,93 mL/kg.min lebih tinggi dibandingkan kontrol 32,09 5,24 mL/kg.min , p = 0,004, serta stres oksidatif menurun MDA eksperimen ? -0,14 0,39 nmol/mL dibandingkan kontrol ? 0,18 0,26 nmol/mL , p = 0,011; SOD eksperimen median ? 0,47 U/mL IQR 0,08-0,74 U/mL dibandingkan kontrol ? 0,14 0,35 U/mL , p = 0,036 . HbA1c kelompok eksperimen menunjukkan penurunan ? -0.43 1.01 , namun tidak bermakna. Skor komposit efek latihan lebih tinggi pada kelompok eksperimen 8,72 1,27 dibandingkan kontrol 7,20 1,08 , p = 0,001.Dengan demikian disimpulkan bahwa program latihan pada penelitian ini memberi manfaat dan dapat diimplementasikan dengan aman. Kata kunci: HIIT dan latihan beban; program latihan berbasis pasien; stres oksidatif; T2DM

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ABSTRACTExercise programs for patients with Type 2 Diabetes Mellitus T2DM must be demonstrably safe, effective, and beneficial. Objectives. In this two-step study, a training program was designed and implemented in a randomized controlled trial RCT to meet the above criteria.The 12-week exercise program combined high intensity interval training HIIT three times per week and resistance training twice weekly , with gradually increased intensity. The HIIT element comprised 1 minute of high intensity exercise HIE and 4 minutes of low intensity exercise LIE . The resistance training element comprised nine exercises for core, upper, and lower extremities. The 42 T2DM patients who participated in the RCT were aged 35 ndash;64 years. Participants were randomly allocated to the experimental EXP group for the new training program and to the control KTR group for continuous cardiorespiratory training. Fitness level VO2max , glycemic control HbA1c , and oxidative stress MDA and SOD were measured before and after the exercise program.VO2max was higher in EXP 38.13 5.93 mL/kg.min than in KTR 32.09 5.24 mL/kg.min; p = 0.004 . Overall oxidative stress decreased in EXP MDA EXP ? -0.14 0.39 nmol/mL as compared to KTR ? 0.18 0.26 nmol/mL; p = 0.011 and SOD EXP median ? 0.47 U/mL IQR 0.08-0.74 U/mL as compared to KTR ? 0.14 0.35 U/mL; p = 0.036 . EXP HbA1c also decreased, although not significantly ? -0.43 1.01 . EXP composite effects score was significantly higher 8.72 1.27 than for KTR 7.20 1.08; p = 0.001 .The exercise program for T2DM patients was shown to be safe, with significant benefits.Keywords: glycemic control; HIIT and resistance training; oxidative stress; patient-based training program; physical fitness; T2DM"

"ABSTRAKMiR-21 diketahui berperan dalam proliferasi dan diferensiasi osteoklas, namun peran ekspresi miR-21 serum pada osteoporosis masih belum jelas. Penelitian sebelumnya mendapatkan bahwa ekspresi miR-21 serum berkorelasi positif dengan densitas mineral tulang pada penderita osteoporosis pascamenopause, tetapi penelitian tersebut tidak menganalisis faktor-faktor lainnya yang terlibat dalam osteoporosis pascamenopause.Penelitian ini bertujuan untuk mengetahui peran ekspresi miR-21 serum, konsentrasi RANKL, OPG, TGF- ? 1, sklerostin, rasio RANKL/OPG, kalsium serum dan aktivitas fisis terhadap densitas mineral tulang belakang pada perempuan pascamenopause hipoestrogenik dengan osteoporosis dibandingkan dengan tanpa osteoporosis, dengan point of interest pada ekspresi miR-21 serum.Penelitian ini dilakukan dengan disain uji potong lintang komparatif, di RSUD Ulin Banjarmasin, pada bulan Agustus 2015 sampai Juli 2016. Subjek dibagi menjadi 2 kelompok yaitu perempuan pascamenopause hipoestrogenik dengan osteoporosis dan tanpa osteoporosis. Pengambilan sampel dilakukan dengan metode consecutive. Pemeriksaan ekspresi miR-21 serum menggunakan metode absolute quantification real-time PCR. Analisis statistik menggunakan uji korelasi Spearman, Mann-Whitney U test dan regresi linear berganda.Subjek dibagi menjadi 2 kelompok yaitu perempuan pascamenopause hipoestrogenik dengan osteoporosis PMOP dan tanpa osteoporosis PMNOP masing-masing sebanyak 60 subjek. Median ekspresi miR-21 serum pada PMOP lebih tinggi secara bermakna dibandingkan dan PMNOP p = 0,001 . Ekspresi miR-21 serum, RANKL, rasio RANKL/OPG dan aktivitas fisis berkorelasi bermakna dengan nilai BMD pada PMOP. Aktivitas fisis sedang berkorelasi negatif bermakna dengan ekspresi miR-21 serum pada PMOP dan PMNOP. Analisis regresi linear berganda menggunakan metode backward stepwise mendapatkan persamaan regresi linear: BMD = 1,373 - 0,085 Ln.miR-21 - 0,176 Log 10.RANKL R2 = 52,5 .Simpulan. Ekspresi miR-21 serum pada perempuan pascamenopsuse hipoestrogenik dengan osteoporosis terbukti lebih tinggi dibandingkan dengan tanpa osteoporosis. Ekspresi miR-21 serum terbukti memberikan pengaruh negatif terhadap nilai BMD tulang belakang pada perempuan pascamenopause hipoestrogenik dengan osteoporosis sebesar 8,5 , dengan persamaan regresi linear BMD = 1,373 - 0,085 Ln.miR-21 - 0,176 Log10.RANKL. Persamaan ini dapat menjelaskan nilai BMD tulang belakang sebesar 52,5 . Kata kunci: BMD, miR-21 serum, Osteoporosis, Pascamenopause

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ABSTRACTMiR-21 is known to play a role in osteoclast proliferation and differentiation, but the role of serum miR-21 expression in osteoporosis remains unclear. Previous research found that serum miR-21 expression was positively correlated with bone mineral density in postmenopausal osteoporosis patients, but the study did not analyze other factors involved in postmenopausal osteoporosis.This study aimed to determine the role of serum miR-21 expression, concentration of RANKL, OPG, TGF- ? 1, sclerostin and serum calcium, RANKL/OPG ratio, and physical activity on bone mineral density of spine in hypoestrogenic postmenopausal women with osteoporosis compared to no osteoporosis, with point of interest on the expression of serum miR-21.This study was conducted by comparative cross sectional design, conducted at Ulin General Hospital Banjarmasin, from August 2015 until July 2016. The subjects were divided into 2 groups of hypoestrogenic postmenopausal women with osteoporosis and without osteoporosis. Sampling was done by consecutive method. Examination of serum miR-21 expression using absolute quantification real-time PCR method. Statistical analysis using Spearman correlation test, Mann-Whitney U test and multiple linear regression.The subjects were divided into 2 groups of hypoestrogenic postmenopausal women with osteoporosis PMOP and without osteoporosis PMNOP each as many as 60 people. Median of serum miR-21 expression at PMOP group was significantly higher compared to PMNOP group p = 0.001 . Serum miR-21 expression, RANKL, RANKL/OPG ratio and physical activity were significantly correlated with BMD values ? ? ? ?in PMOP group. Moderate physical activity was significantly negative correlated with serum miR-21 expression. Multiple linear regression multivariate analysis using backward stepwise method obtained linear regression equation BMD = 1,373 - 0,085 Ln.miR-21 - 0,176 Log10.RANKL R2 = 52,5 .Conclusion. Serum miR-21 expression in hypoestrogenic postmenopausal women with osteoporosis has been shown to be higher compared with no osteoporosis. Serum miR-21 expression proved to have a negative effect on spinal BMD values in hypoestrogenic postmenopausal women with osteoporosis of 8.5 , with linear regression equation BMD = 1.373 - 0.085 Ln.miR-21 - 0.176 Log10.RANKL. This equation can explain the value of spinal BMD by 52.5 . Keywords: BMD, Osteoporosis, postmenopausal, serum miR-21 "

"ABSTRAKTriglyceride Glucose Index Merupakan Prediktor MarkerDiagnostik Konversi Prediabetes Yang Akurat Pada Wanita Urban Usia ReproduktifAbstrakPertimbangan epidemiologis memberi bukti bahwa banyak wanita usia reproduktif menderitaprediabetes atau diabetes, yang mengakibatkan lebih banyak kehamilan dengan ibu dan janinyang berisiko tinggi mengalami komplikasi. Penilaian resistensi insulin merupakan fundamentalgoal yang mempunyai nilai prevensi besar. Triglyceride Glucose Index TyG Index merupakanmarker surrogate resistensi insulin yang dapat diaplikasikan pada komunitas sebagai metodeskrining praktis dan efisien. Penelitian ini bertujuan untuk mengetahui insiden, nilai prediksi,ukuran dampak potensial, serta pengaruh perubahan TyG Index yang dinamis terhadap konversistatus glukosa darah yang terjadi pada wanita urban usia reproduktif. Desain penelitian ini adalahPrevalence Longitudinal Study. Data dianalisis dengan deskriptif, Receiver OperatingCharacteristic, Cox Regression dan Multi-State Survival Model. Hasil penelitian menunjukkanbahwa setelah 5 tahun follow up pada 371 subjek prediabetes, insiden konversi progresivitasdiabetes sebesar 21 , 36,9 tidak konversi, dan 42 regresivitas menjadi normoglikemik.Sedangkan pada 1300 subjek normoglikemik, insiden progresivitas diabetes 2,4 , 21,6 progresivitas prediabetes, dan 76 tidak konversi. Cut off point TyG Index dalam memprediksikonversi pada subjek prediabetes dalam 5 tahun adalah 4,54 subjek progresivitasmenjadi diabetes. Sedangkan, pada subjek normoglikemik, cut off point TyG Index le;4,43 subjektetap normoglikemik; 4,44 - 4,47 subjek progresivitas menjadi prediabetes; dan >4,47 subjekprogresivitas menjadi diabetes. Hazard ratio TyG Index terhadap regresivitas normoglikemikadalah 0,242 95 CI = 0,135 ndash; 0,433 setelah diadjusted lingkar perut. Sedangkan hazard ratioTyG Index terhadap konversi progresivitas diabetes pada subjek normoglikemik adalah 2,169 95 CI = 1,006 ndash; 4,678 setelah diadjusted lingkar perut, HDL, dan sistolik. Ukuran dampakpotensial AR TyG Index pada subjek prediabetes adalah 80,67 , sedangkan pada subjeknormoglikemik 70,17 . Analisis Multi-State Survival Model menunjukan peningkatan TyGindex, kolesterol total, LDL, lingkar perut, dan diastolik yang dinamis berpengaruh positifterhadap konversi progresivitas menjadi diabetes.Kata kunci: Konversi, Prediabetes, TyG Index

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ABSTRACTTriglyceride Glucose Index is an Accurate Diagnostics Predictor Markerof Prediabetes Conversion in Urban Reproductive WomenAbstractEpidemiological considerations provide evidence that many women of reproductive age sufferfrom prediabetes or diabetes, which leads to more pregnancies with mothers and fetuses at highrisk of complications. Assessment of insulin resistance is a fundamental goal that has a greatvalue for prevention. Triglyceride Glucose Index TyG Index is a surrogate insulin resistancethat can be applied to the community as a screening method to predict the conversion of bloodglucose status practically and efficiently. This study aims to determine the incidence, predictionvalue, the attributable risk, and the effect of dynamic TyG Index changes on the statusconversion that occurs in urban reproductive women. The design of this study was PrevalenceLongitudinal Study, in which all cases that occurred at the beginning of the study were included.Data were analyzed by descriptive, Receiver Operating Characteristic, Cox Regression andMulti-State Survival Model. The results showed, after 5 years of follow-up on the prediabetes371 subject, the incidence of diabetes progression was 21 , 36.9 was not conversion, and 42 regressive to normoglycemic. Whereas in 1,300 normoglycemic subjects, the incidence ofdiabetes progression 2.4 , prediabetes progression 21.6 , and 76 was not conversion. The cutoff point of TyG Index in predicting the conversion in the prediabetes subject within 5 years was4.54 subjects were diabetes progression. Whereas, in the normoglycemic subject, the cut offpoint of TyG Index le;4.43 remains normoglycemic; 4.44 - 4.47 the subject rsquo;s progression toprediabetes; and> 4.47 the subjects of progression to diabetes. The hazard ratio of TyG Index tonormoglycemic regression is 0.242 95 CI = 0.135 - 0.433 adjusted by abdominalcircumference. While the hazard ratio of TyG Index to diabetes progression in normoglycemicsubjects was 2,169 95 CI = 1.006 - 4,678 adjusted by abdominal circumference, HDL, andsystolic. The attributable risk of the TyG Index on the prediabetes subject was 80.67 , whilein the normoglycemic subjects 70.17 . Analysis of Multi-State Survival Model showed increaseof TyG index, total cholesterol, LDL, abdominal circumference, and diastolic which is positivetoward progress to diabetes.Keywords: Conversion, Prediabetes, TyG Index"

"Prediabetes adalah toleransi glukosa terganggu, kadar glukosa darah puasa berkisar dari 100- 125 mg/dl dan kadar glukosa darah 2 jam pasca pembebanan 75 gr berkisar 140-199 mg/dl. Skrining pada prediabetes diperlukan dapat rangka pengobatan dini serta pencegahan komplikasi. Peningkatan lingkar perut meningkatkan risiko mengalami kondisi prediabetes Penelitian ini bertujuan menganalisis pengaruh obesitas sentral terhadap kejadian prediabetes. Pendekatan studi menggunakan desain kohort retrospektif. Diagnosis obesitas sentral menggunakan ukuran lingkar perut pria: ³ 90 cm wanita: ³ 80 cm sedangan diagnosis prediabetes menggunakan kadar gula darah pasca pembebanan 75 gr: 140-199 mg/dL dengan data studi kohor faktor risiko PTM yang dikelola oleh Balitbangkes Kemenkes RI di Kecamatan Bogor Tengah dalam enam tahun pemantauan. Hasil penelitian ini menunjukkan bahwa iniden kumulatif : 31,4% dan insiden rate: 49 per 1000 orang/tahun. Analisis bivariat menunjukkan terdapat pengaruh yang bermakna secara statistik antara obesitas sentral dengan kejadian prediabetes dengan HR: 1,67 (95% CI: 1,42 -1,97) dengan p-value = < 0,00. Pengaruh yang bermakna secara statistik antara obesitas sentral terhadap kejadian prediabetes dengan nilai 1,7 (95% CI 1,1-2,4) p-value = < 0,001 setelah dikontrol oleh variabel counfounder yaitu IMT dan adanya interaksi dengan variabel trigliserida dan status perkawinan. Trigliserida dan status perkawinan memberikan pengaruh pada obesitas sentral terhadap kejadian prediabetes. Trigliserida pada kategori kadar trigliserida tinggi nilai HR 1,7 (1,1-2,4). Status perkawinan pada kategori tidak menikah/janda/duda berkontribusi dalam meningkatkan risiko prediabetes untuk responden yang memiliki obesitas sentral dengan nilai HR 1,8 (95% CI: 1,2-2,9). Rekomendasi pencegahan prediabetes dilakukan dengan pemeriksaan trigliserida pada obesitas sentral supaya prognosis tidak jelek dan mudah diintervensi untuk dapat kembali ke keadaan normal.

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Prediabetes is defined by a reduced ability to process glucose, with fasting blood glucose levels between 100-125 mg/dl and 2-hour post-load blood glucose levels of 140-199 mg/dl following the consumption of 75 grams of glucose. Early detection and treatment of prediabetes through screening is crucial in order to avert problems. An increase in waist circumference increases the risk of developing prediabetes. The study revealed that an increase in waist circumference is directly linked to a greater likelihood of developing prediabetes. The objective of this study is to examine the impact of central adiposity on an individual's ability to resist the development of prediabetes. The study employed a retrospective cohort design. The diagnosis of central obesity was established based on waist circumference measurements, with a threshold of ≥ 90 cm for men and ≥ 80 cm for women. Prediabetes was diagnosed by analyzing post-load blood glucose levels (ranging from 140-199 mg/dL) obtained from the 75-gram glucose load test. These diagnostic criteria were derived from a six-year monitoring of a cohort study on non-communicable disease risk factors, which the Health Research and Development Agency conducted under the Ministry of Health of the Republic of Indonesia in Central Bogor District.

The results of this study show a cumulative incidence of 31.4% and an incidence rate of 49 per 1000 people/year. Bivariate analysis indicated a statistically significant association between central obesity and the incidence of prediabetes, with an HR of 1.67 (95% CI: 1.42-1.97) and a p-value ≤ 0.00. After controlling for confounding variables such as BMI and interactions with triglyceride levels and marital status, central obesity remained significantly associated with the incidence of prediabetes, with an HR of 1.7 (95% CI: 1.1-2.4) and a p-value ≤ 0.001. Triglyceride levels and marital status influenced the impact of central obesity on the incidence of prediabetes. High triglyceride levels had an HR of 1.7 (1.1-2.4), while being unmarried/widowed/divorced contributed to an increased risk of prediabetes in respondents with central obesity, with an HR of 1.8 (95% CI: 1.2-2.9). The recommendation is that prevention of prediabetes should involve monitoring triglyceride levels in individuals with central obesity to improve prognosis and facilitate interventions aimed at returning to a normal state."