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"Coronary artery disease (CAD) is an important cause of death in end-stage renal disease (ESRD) patients on regular hemodialysis. The high risk of CAD occurrence in ESRD patients is partially due to a high prevalence of established atherosclerotic risk factors, which are hypertension, diabetes and dyslipidemia. However, unique renal-related risk factors are also likely to contribute to this high risk of CAD. The high prevalence of hyperhomocysteinemia in ESRD patients is of interest because of the probable cardiovascular risk associated with the increase of total plasma homocysteine concentration. The aim of this study was to evaluate the role of homocysteine as a risk factor for CAD in non-diabetic ESRD patients on regular hemodialysis.
Total fasting plasma homocysteine, total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, hypertension and smoking habit were documented from 80 non-diabetic ESRD patients on regular hemodialysis (48 men, 32 women; mean age 54.5±6.5 years). Twenty-two (27.5%) among these patients suffered from CAD according to ECG and echocardiographic criteria. The risk of CAD was analyzed using a stepwise multiple logistic regression. Total fasting plasma homocysteine concentration and other risk factors for CAD were also determined in 80 age- and sex-matched normal controls.
Total fasting plasma homocysteine concentration was significantly higher in non-diabetic ESRD patients than in normal controls (26.0±1.5 versus 14.6±1.3 fimol/L; p<0.01). Hyperhomocysteinemia was observed in 92.5% ESRD patients. Homocysteine concentration was significantly higher in ESRD patients with CAD than without CAD (33.8±1.4 versus 23.5+1.5 umol/L; p<0.01). High total plasma homocysteine concentration and hypertension were independently associated with CAD in non-diabetic ESRD patients on regular hemodialeine concentration in the upper tertile (>30.6 jxmol/L) had an adjusted odds ratio of 2.95 (CI, 1.02 to 8.53; p<0.05). In ESRD patients, the intake of folic acid is the only factor associated with total plasma homocysteine concentration. The increase of total plasma homocysteine concentration in normal controls was associated with increased age and smoking habit.
This study concludes that a high total plasma homocysteine concentration is an independent risk factor for coronary artery disease in non-diabetic ESRD patients on regular hemodialysis."
2003
AMIN-XXXV-1-JanMarc2003-9
Artikel Jurnal  Universitas Indonesia Library
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Yanuar Indah Pratiwi
"Homosistein (Hcy) adalah asam amino yang mengandung tiol dan memiliki potensi sebagai penanda biologis dari komplikasi terkait diabetes melitus tipe 2, seperti makrovaskular dan mikrovaskular. Tujuan dari penelitian ini adalah untuk mengetahui perbandingan homosistein serum pada pasien diabetes melitus tipe 2 dengan terapi metformin dan kombinasi metformin-glimepirid. Penelitian dilakukan dengan desain potong lintang dengan metode consecutive sampling di Puskesmas Kecamatan Pasar Minggu dan Puskesmas Depok Jaya. Sampel darah subjek penelitian dikumpulkan untuk pengukuran HbA1c dan kadar homosistein serum. Kadar homosistein serum diukur menggunakan Axis® Homocysteine EIA Kit. Total 125 partisipan dibagi menjadi dua kelompok yaitu pengguna terapi metformin (n=57) dan kombinasi metformin-glimepirid (n=68). Tidak terdapat perbedaan yang bermakna secara statistik pada karakteristik dasar dan klinis kedua kelompok kecuali regimen terapi (metformin) (p=0,003). Tidak terdapat perbedaan yang bermakna (p=0,163) pada hasil pengukuran kadar homosistein serum pada kelompok metformin (12,03±3,45) dan kombinasi metformin-glimepirid (13,08±4,69). Hiperhomosisteinemia (µmol/L) lebih banyak ditemukan pada kelompok kombinasi metformin-glimepirid dibandingkan dengan kelompok metformin, namun tidak bermakna secara statistik (p=0,113). Terdapat faktor yang dapat memengaruhi kadar homosistein yaitu jenis kelamin, durasi menderita DMT2, rutinitas olahraga, dan regimen terapi (glimepirid). Oleh karena itu dapat disimpulkan bahwa tidak terdapat perbedaan kadar homosistein serum pada kelompok metformin dan kombinasi metformin-glimepirid.

Homocysteine (Hcy) is an amino acid that contains thiols and has the potential to be a biological marker of complications related to type 2 diabetes mellitus, such as macrovascular and microvascular. The purpose of this study was to determine the comparison of serum homocysteine in type 2 diabetes mellitus patients with metformin and metformin-glimepiride combination therapy. The study was conducted with a cross-sectional design with a consecutive sampling method at the Pasar Minggu Subdistrict Health Center and the Depok Jaya Health Center. Blood samples of the research subjects were collected for measurements of HbA1c and serum homocysteine levels. Serum homocysteine levels were measured using the Axis® Homocysteine EIA Kit. A total of 125 participants were divided into two groups, users of metformin therapy (n=57) and metformin-glimepiride combinations (n=68). There were no statistically significant differences in baseline and clinical characteristics among groups except for therapeutic regimen (metformin) (p=0,003). There was no significant difference (p=0,163) in the measurement results of serum homocysteine levels in the metformin (12,03±3,45) and metformin-glimepiride combination (13,08±4,69). Hyperhomocysteinemia (μmol/L) was more commonly found in the metformin-glimepiride combination group compared to the metformin group, but was no statistically significant difference (p=0.113). Gender, duration of T2DM, regular exercise, and therapeutic regimen (glimepiride) are factors that can affect homocysteine levels. Therefore, it can be said that there was no difference in serum homocysteine levels in the metformin and metformin-glimepiride groups.
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Depok: Fakultas Farmasi Universitas Indonesia, 2022
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UI - Skripsi Membership  Universitas Indonesia Library
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Marcel Antoni
"Latar belakang: Vitamin B12 merupakan kofaktor enzimmetionin sintase yang berperan pada
proses remetilasi homosistein menjadi metionin sehingga, mencegah akumulasi homosistein
(hiperhomosisteinemia). Defisiensi vitamin ini dapat menyebabkan terjadinya
hiperhomosisteinemia dan memicu stres oksidatif yang menyebabkan resistensi insulin.
Penelitian ini bertujuan untuk mengetahui apakah resistensi insulin yang diinduksi restriksi
vitamin B12 dapat menurunkan kontrol insulin terhadap proses glukoneogenesis melalui
pensinyalan FOXO1 dan ekspresi gen targetnya, G6Pc.
Metode: Penelitian ini menggunakan 24 jaringan hati tersimpan tikus jantan Spraque-Dawley,
berusia 36-40 minggu; yang terbagi dalam 4 kelompok: kelompok kontrol dan kelompok
perlakuan yang diberi pakan khusus restriksi vitamin B12 selama 4, 8, dan 12 minggu. Semua
sampel jaringan yang digunakan dalam penelitian ini merupakan sampel jaringan yang sama,
yang digunakan dalam penelitian oleh Sianipar, dkk, berjudul “Dampak Restriksi Vitamin B12
Terhadap Kadar Homosistein, HOMA-IR, dan Gambaran Histopatologi Perlemakan Hati Non-
Alkoholik Pada Tikus”. Terhadap 24 sampel jaringan hati tersebut dilakukan pemeriksaan
Western Blot untuk membandingkan aktivitas protein FOXO1 dan pemeriksaan real time-PCR
untuk membandingkan ekspresi gen G6Pc antar kelompok sampel.
Hasil: Tidak terdapat perbedaan bermakna, baik aktivitas protein FOXO1 maupun ekspresi
gen G6Pc antara kelompok restriksi vitamin B12 dengan kelompok kontrol.
Kesimpulan: Pada keadaan resistensi insulin yang dipicu oleh hiperhomosisteinemia, pada
kondisi restriksi vitamin B12, proses glukoneogenesis tergantung insulin melalui inhibisi jalur
pensinyalan FOXO1 dan G6Pc tidak berbeda dibandingkan kelompok kontrol. Penelitian lebih
lanjut dibutuhkan untuk melihat kemungkinan apakah hiperglikemia pada kondisi ini dapat
disebabkan melalui jalur lain atau adanya penurunan utilisasi glukosa dan proses glikogenesis

Background: Vitamin B12 is a cofactor of the enzyme methionine synthase which plays a role
in the remetilation process of homocysteine to methionine so as to prevent the accumulation of
homocysteine (hyperhomocysteinemia). Deficiency of this vitamin can cause
hyperhomocysteinemia and trigger oxidative stress which causes insulin resistance. This study
aims to determine whether insulin resistance induced restriction of vitamin B12 can reduce
insulin control of gluconeogenesis through FOXO1 signaling and the expression of its target
gene, G6Pc.
Methods: This study used 24 stored liver tissue of Spraque-Dawley male rats, aged 36-40
weeks; divided into 4 groups: the control group and the treatment group who were given special
food restriction of vitamin B12 for 4, 8, and 12 weeks. All tissue samples used in this study
were the same tissue samples, which were used in a study by Sianipar, et al., titled "The Impact
of Vitamin B12 Restriction on Homocysteine, HOMA-IR, and Histopathological Descriptions
of Non-Alcoholic Fatty Liver in Mice". Western Blot tests were performed on 24 liver tissue
samples to compare FOXO1 protein activity and real time-PCR examination to compare G6Pc
gene expression between sample groups.
Results: There was no significant difference, either the FOXO1 protein activity or G6Pc gene
expression between the vitamin B12 restriction group and the control group.
Conclusion: In a state of insulin resistance triggered by hyperhomocysteinemia, under
conditions of vitamin B12 restriction, gluconeogenesis depends on insulin through the
inhibition of the FOXO1 signaling pathway and G6Pc no different than the control group.
Further research is needed to see the possibility of whether hyperglycemia in this condition can
be caused by other pathways or by a decrease in glucose utilization and the process of
glycogenesis.
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Depok: Fakultas Kedokteran Universitas Indonesia, 2020
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UI - Tesis Membership  Universitas Indonesia Library