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Lestari Octavia
Abstrak :
Latar belakang: Enzim methylenetetrahydrofolate reductase (MTHFR) terlibat dalam metabolism asam folat dan tipe allele mempengaruhi aktivitas enzim. Memberikan suplementasi asam folat kepada ibu hamil dapat mempengaruhi perubahan dalam derajat metilasi gen tertentu yang mempengaruhi kesehatan janin. Walaupun sudah banyak penelitian yang mempelajari peran asam folat sebagai donor dalam mekanisme epigenetik, namun penelitian pengaruh suplementasi besi-asam folat pada luaran kehamilan melalui pendekatan interaksi zat gizi-gen dalam desain penelitian longitudinal masih jarang. Penelitian ini bertujuan untuk mengetahui hubungan antara kadar serum asam folat pada ibu dan anak, dan derajat metilasi pada gen pencetak insulin-like growth factor (IGF2) yang dikenal terlibat dalam tumbuh kembang anak dan dapat digunakan sebagai penanda kemunculan penyakit Metode: Di tahun 2018, penelitian longitudinal dilakukan dengan mengunjungi 127 subyek termasuk anak yang dilahirkan dan mengikutsertakannya dalam penelitian. Enam puluh tujuh serum asam folat ibu selama hamil dan pasca melahirkan diperiksa, sementara serum asam folat anak dikumpulkan sebanyak 44 spesimen untuk pemeriksaan penanda darah. Pemeriksaan serum asam folat dengan menggunakan the liquid chromatography-mass spectrometry/mass spectrometry. Untuk pemeriksaan biomolekuler, tipe allele enzim MTHFR 677C>T and 1298A>C menggunakan Taqman polymerase chain reaction. Sementara metode pyrosequencing digunakan untuk menghitung DNA metilasi pada IGF2 pada anak. Hubungan antar variabel dianalisis menggunakan analisis regresi linier multivariat. Hasil:Tidak ada hubungan yang signifikan antara asupan asam folat dan serum asam folat ibu selama hamil, tiga tahun pasca melahirkan dan anak yang dilahirkan (p>0.05). Penelitian ini tidak dapat menunjukkan hubungan antara tipe allel dari MTHFR 677 C>T dan 1298 A>C dan serum asam folat (p>0.05). Serum asam folat selama hamil juga mempengaruhi status serum asam folat tiga tahun pasca melahirkan (p<0.05) dan status serum asam folat anak (p<0.05). Namun penelitian ini tidak dapat menunjukkan pengaruh status serum asam folat anak dengan DNA metilasi IGF2 pada anak (p>0.05). Simpulan: Serum asam folat selama hamil berkontribusi pada serum asam folat tiga tahun pasca melahirkan dan anak. Genotipe dari MTHFR gene at 677C>T and 1298 A>C kemungkinan tidak terlibat dalam metabolism asam folat pada ibu. Serum asam folat selama kehamilan tidak memiliki dampak pada status metilasi dari IGF2 pada wilayah differentially methylated region (DMR) untuk subyek anak. Namun, beberapa hal harus menjadi perhatian karena, secara statistik, jumlah subyek penelitian tidak memadai. Saran: Perlu dilakukan penelitian lanjutan yang melibatkan subyek lebih banyak dan metode yang lebih canggih dalam menentukan MTHFR dan metilasi DNA. ...... Background: Methylenetetrahydrofolate reductase, (MTHFR) enzyme is involved in folic acid metabolism, and their allele types affected its activity. Providing folic acid supplementation to pregnant mothers may influence the change in methylation level in specific genes that affect the susceptibility of disease of their offspring. Although folic acid's role as a donor in the epigenetic mechanism has been investigated, a longitudinal study exploring the influence of iron-folic acid supplementation on maternal dan birth outcome by the nutrient-gene interaction approach is lacking. Therefore, we investigated the relationship of serum folic acid level among the mothers and the children, and the imprinted insulin-like growth factor 2 (IGF2) methylation level that is known actively involved in growth and development in children and possibly utilized as a surrogate marker for the disease Methods: In 2018, the follow-up study conducted by re-visited 67 subjects and put the mother and their children included in the study. For each group, sixty-seven serums were collected for folic acid measurement for mothers during gestation and three-year post-partum. Furthermore, forty-four serums for children were gathered for biomarker measurement. Serum folics were measured by using liquid chromatography-mass spectrometry/mass spectrometry. Determining the genotype of the MTHFR enzyme in position 677C>T and 1298 A>C was used Taqman Polymerase Chain Reaction (PCR) method. The pyrosequencing method was utilized to quantify the methylation level of the IGF-2 of the children. The relationship analysis between variables using multivariate linear regression. Results: There was no relationship between the folic acid intake during gestation and serum folic acid of the mothers during pregnancy, three-year post-partum, and the children (p>0.05). There was no relationship between the allele type of MTHFR 677C>T and 1298A>C and serum folic acid status of the mother (p>0.05). The serum folic acid during pregnancy had a significant relationship to the serum folic acid three-year post-partum (p<0.05) as well as the serum folic acid of the children (p<0.05). There was no significant relationship between the serum folic acid of the children, serum homocysteine, and the methylation status of IGF2 of the children (p>0.05). Conclusion: The serum folic acid during pregnancy contributed to the serum folic acid three-year post-partum of mother and the children. The genotype of the MTHFR gene at 677C>T and 1298 A>C was possibly not involved in folic acid metabolism in the mother. Serum folic acid during pregnancy could not have an effect on the methylation status of the IGF2 in the differentially methylated region (DMR) area of the children. However, this conclusion needs to be taken in caution due to lack of study power Recommendation: Further cohorts studies with a large sample size and more advanced methods in determining the MTHFR enzyme and DNA methylation. Keyword: serum folic acid, genotyping MTHFR 677 C>T, MTHFR 1298 A>C, DNA methylation, IGF2.
Depok: Fakultas Kedokteran Universitas Indonesia, 2021
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Patricia Budi Hartanti Liman
Abstrak :

Carborxymethyl lysine dalam makanan (dCML), CML plasma (pCML), dan tumor necrosis alpha plasma (pTNF-α) mungkin dapat memengaruhi obesitas. Namun database kandungan CML makanan di Indonesia dan penelitian tentang pengaruh asupan CML terhadap obesitas pada wanita Asia belum pernah dilaporkan sebelumnya.

Penelitian ini bertujuan untuk mendapatkan database CML makanan Indonesia dan menilai efek mediator dCML, pCML, dan pTNF-α terhadap lingkar pinggang (WC), rasio lingkar pinggang terhadap tinggi badan (WHtR), dan indeks masa tubuh (IMT).

Penelitian potong lintang dilakukan terhadap 235 wanita sehat berusia 19-50 tahun, yang bertempat tinggal di daerah pesisir pantai dan pegunungan di Sumatra Barat dan Jawa Barat. Database CML dibuat berdasarkan estimasi dari database CML yang telah dipublikasi dan pemeriksaan secara langsung pada makanan yang diambil dari kedua provinsi tersebut, dengan menggunakan metode liquid chromatography-tandem mass spectrometry. Asupan CML, pCML, dan pTNF-α didapatkan berturut-turut dari 2x24 jam recalls, ultra-performance liquid chromatography-tandem mass spectrometry, and enzyme-linked immunosorbent assay. Perbedaan di antara kelompok dianalisis dengan menggunakan Chi-square atau t-test tidak berpasangan, efek mediator dianalisis dengan structural equation modelling, dan untuk perilaku makan dilakukan dengan wawancara mendalam dan observasi.

Terdapat 161 dari 252 jenis makanan dalam database CML yang telah diidentifikasi kandungan CMLnya secara langsung. Kelompok daging dan kacang-kacangan memiliki nilai rerata kandungan CML tertinggi pertama dan kedua. Geometric means ± SD dari dCML, pCML, dan pTNF-α berturut-turut sebesar 1.7±0.8 mgCML/hari, 22.3±7.9 ng/mL, dan 0.68 ± 0.38 IU/mL. Asupan CML berhubungan langsung dan positif terhadap pCML (β= 0.99 [95%CI: 0.53, 1.78]) demikian pula pCML terhadap pTNF-α (β= 0.12 [95%CI: 0.28, 0.49]). Plasma CML dan pTNF-α berhubungan secara langsung dan positif terhadap WC (β= 0.21 [95%CI: 0.08, 0.33] dengan β= 0.23 [95%CI: 0.11, 0.35]) dan juga terhadap WHtR (β= 0.18 [95%CI: 0.06, 0.31] dengan β= 0.23 [95%CI: 0.11, 0.35]). Pada wawancara mendalam didapatkan bahwa kelompok suku Sunda lebih banyak mengosumsi makanan yang diproses seperti ikan peda goreng, ikan asin goreng dan bakso dibandingkan kelompok suku Minangkabau.

Simpulan: Asupan CML, pCML, dan pTNF-α tampaknya lebih berperan sebagai mediator terhadap WC dan WHtR, dibandingkan terhadap BMI. Pembatasan asupan CML diperlukan untuk menurunkan risiko obesitas sentral pada populasi ini.


Carborxymethyl lysine in foods (dCML), plasma CML (pCML), and plasma tumor necrosis alpha (pTNF-α) may have an influence on obesity. However, there have been no reports on databases of CML content in Indonesian foods and on studies of the influence of CML intake on obesity in Asian women.

This study aims to develop a database of CML content in Minangkabau and Sundanese foods and to evaluate the mediator effects of dCML, pCML, and pTNF-α on waist circumference (WC), waist to height ratio (WHtR), and body mass index (BMI).

A cross-sectional study was conducted in 235 healthy women aged 19-50 years, who resided in coastal and mountainous areas of West Sumatra and West Java. The CML database was developed based on an estimate from published database and direct measurement of foods obtained from these two provinces, using liquid chromatography-tandem mass spectrometry. The dCML, pCML, and pTNF-α concentrations were obtained from 2x24 hour recalls, ultra-performance liquid chromatography-tandem mass spectrometry, and enzyme-linked immunosorbent assay, respectively. Between-group differences were analyzed by chi-square test or unpaired t-test, the mediator effects by structural equation modelling, and eating behavior by in-depth interviews and observations.

There were 161 of 252 food items of which the CML content was determined. The group of meats and the group of legumes had the highest and second highest mean CML content, respectively. The Geometric means ± SD of dCML, pCML, and pTNF-α were 1.7±0.8 mgCML/day, 22.3±7.9 ng/mL, and 0.68 ± 0.38 IU/mL, respectively. There was a direct positive association between dCML and pCML (β= 0.99 [95%CI: 0.53, 1.78]) and between pCML and pTNF-α (β= 0.12 [95%CI: 0.28, 0.49]). Plasma CML and pTNF-α were directly and positively associated with WC (β= 0.21 [95%CI: 0.08, 0.33] and β= 0.23 [95%CI: 0.11, 0.35]) and WHtR (β= 0.18 [95%CI: 0.06, 0.31] and β= 0.23 [95%CI: 0.11, 0.35]). In eating behavior, it was seen that the Sundanese women consumed more CML from processed foods such as fried fermented fish (ikan peda goreng), fried salted fish (ikan asin goreng) and meatballs (bakso) than Minangkabau women.

Conclusion: Dietary CML, pCML, and pTNF-α apparently had a greater role as mediators in the path from ethnicity to WC and WHtR, than in the path from ethnicity to BMI. Limitation of CML intake is necessary to reduce the risk of central obesity in this population

Depok: Fakultas Kedokteran Universitas Indonesia, 2020
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Gusnedi
Abstrak :

LATAR BELAKANG: Praktik diet yang kurang memadai berdampak negatif terhadap asupan zat gizi dan kejadian penyakit kronis yang berhubungan dengan gizi. Penelitian ini bertujuan untuk mengembangkan Panduan Gizi Seimbang Berbasis Pangan Lokal (PGS-PL) berdasarkan pola makan masyarakat Minangkabau, dalam rangka perbaikan asupan gizi pada wanita usia subur (WUS) penderita dislipidemia. Selanjutnya pada tahap intervensi, dilihat efek promosi PGS-PL terhadap perubahan praktik diet, asupan zat gizi, status gizi dan profil lipid pada WUS Minangkabau dengan dislipidemia.

METODE: Studi tahap pertama menggunakan disain potong lintang, melibatkan 74 WUS suku Minangkabau dengan dislipidemia. Berdasarkan pola makan setempat, identifikasi problem nutrient dan penyusunan PGS-PL dilakukan dengan pendekatan Linear programming, menggunakan tiga dari empat modul pada software Optifood yang dikembangkan oleh WHO. Pada tahap ke dua dilakukan studi intervensi komunitas menggunakan disain pengukuran sebelum dan sesudah dengan kelompok kontrol. Subjek penelitian ditempatkan secara acak yang dikluster ke dalam kelompok PGS-PL (mendapatkan promosi PGS-PL selama 12-minggu) atau kelompok non-PGS-PL (mendapatkan satu kali konsultasi gizi dari pelayanan kesehatan tingkat dasar). Sebanyak 102 WUS (48 pada kelompok PGS-PL dan 54 pada kelompok non-PGSPL) selama 12 minggu. Pada akhir studi, analisis perbedaan antar- dan inter kelompok perlakuan dilakukan untuk melihat perubahan praktik diet, asupan zat gizi, status gizi dan profil lipid darah (kadar kolesterol total, Lipoprotein densitas rendah, Lipoprotein densitas tinggi, dan Trigliserid).

HASIL: Berdasarkan pola makan setempat, ditemukan bahwa asam lemak tidak jenuh (polyunsaturated fatty acid/PUFA, n-3, n-6), serat makanan, zat besi, dan seng merupakan problem nutrient pada WUS suku Minangkabau dengan dislipidemia. PGS-PL yang disusun menekankan penggabungan bahan makanan, kelompok atau sub-kelompok bahan makanan bernilai gizi tinggi yang tersedia secara lokal, untuk meningkatkan asupan problem nutrient tersebut. Promosi PGS-PL dapat meningkatkan skor praktik diet secara bermakna. Peningkatan terutama terjadi pada konsumsi makanan dan sub-kelompok makanan yang dipromosikan (ikan laut, unggas, produk kedelai seperti tahu dan tempe, total sayuran, sayuran hijau, buah-buahan, dan kentang). Tidak ada perubahan bermakna pada konsumsi makanan pokok, makanan selingan, telur, dan makanan yang digoreng pada akhir intervensi. Pengaruh promosi PGS-PL pada asupan zat gizi dapat dilihat pada perubahan yang bermakna pada asupan energi dan karbohidrat, persentase energi dari PUFA dan monounsaturated fatty acid (MUFA), serta rasio PUFA terhadap asam lemak jenuh (saturated fatty acids/SAFA) dalam makanan sehari-hari. Namun, asupan lemak jenuh tidak berubah signifikan. Terdapat perbaikan yang bermakna pada berat badan, indeks massa tubuh, dan lingkar pinggang, namun tidak bermakna terhadap penurunan prevalensi obesitas. Tidak terdapat perubahan profil lipid darah yang bermakna setelah intervensi.

KESIMPULAN: Pendekatan linier programming dapat digunakan dalam menyusun PGS-PL untuk meningkatkan praktik diet dan asupan problem nutrient pada WUS dengan dislipidemia. Promosi PGS-PL secara bermakna berdampak terhadap peningkatan praktik diet, asupan zat gizi, dan status gizi, tetapi belum berpengaruh secara statistik terhadap perbaikan profil lipid WUS dengan dislipidemia.


BACKGROUND: Given the impact of unfavorable dietary practices is on inadequate nutrient intake and nutrition-related chronic diseases, we sought the problem nutrient in the community habitual dietary practices, and developed an optimized food-based recommendation (FBR) for Minangkabau women of reproductive age (WoRA) with dyslipidemia. Although the effect of the FBR promotion seemed to be potential at planning phase, but this has not been tested in the community setting. Therefore, we conducted a community trial and explored the effect of FBR promotion using locally available foods on dietary practice, nutrient intakes, nutritional status and lipid profile among Minangkabau WoRA with dyslipidemia.

METHODS: The first stage of the study was a cross-sectional study, which involved 74 Minangkabau WoRA with dyslipidemia. Linear programming analysis using three modules of the WHO Optifood software was employed to identify problem nutrients and develop an optimized FBR. The second phase of the study was a community-based trials using pre-post with control group design. The subjects were cluster randomized into either FBR group (receiving 12-weeks of FBR promotion) or non-FBR group (receiving once standard nutritional counseling from primary health care program). At the end, 102 WoRA (48 and 54 WoRA in the FBR group and the non-FBR group, respectively) completed 12-weeks of intervention. We analyzed within- and between group differences on changes of dietary practices, nutrient intakes, nutritional status and lipid profile (serum Total Cholesterol, Low-Density Lipoprotein, High-Density Lipoprotein and Triglyceride levels) at the completion of the study.

RESULTS: Our results identified PUFA, dietary fiber, iron, and zinc as problem nutrients among Minangkabau WoRA with dyslipidemia. The final food-based recommendations emphasized the incorporation of locally available nutrient-dense foods, food groups, and sub-groups that would improve the intake of the identified problem nutrients. The FBRs promotion significantly increased the overall dietary compliance. An increase was predominantly occurred on the consumption of promoted and subgroups food items (sea fish, poultry, soybean products, total vegetables, dark green leafy vegetables, fruits, and potato). There were no significant changes in the consumption of staple food, snacks, eggs, and fatty foods at the end of intervention.  Effect of FBR promotion on nutrient intake was observed through the significant changes in energy and carbohydrate intakes, percentage of energy from PUFA and MUFA, as well as PUFA to SAFA ratio in daily diet. However, intake of saturated fat remained unchanged. Marginal but significant improvements were observed in body weight, BMI, and waist circumference, but the prevalence of obesity was relatively not affected. There were no significant changes of blood lipid profile at the end of intervention.

CONCLUSIONS: Linear programming approach could be potentially used to develop an optimized food-based recommendation based on the identified problem nutrients and locally available nutrient dense foods. The FBRs promotion produced significant improvement in dietary practice, nutrient intakes, and nutritional status, but did not statistically affect blood lipid profile of Minangkabau WoRA with dyslipidemia. 

Depok: Fakultas Kedokteran Universitas Indonesia, 2020
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UI - Disertasi Membership  Universitas Indonesia Library