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"Diabetes melitus tipe 2 (DMT2) adalah penyakit gangguan metabolisme yang menyebabkan regulasi insulin terganggu dan dapat mengakibatkan komplikasi penyakit ginjal diabetes (PGD). Saat ini, gold standard penilaian fungsi ginjal dilakukan berdasarkan parameter eGFR dan albuminuria, tetapi kedua parameter tersebut memiliki beberapa keterbatasan. Oleh karena itu, metode baru untuk deteksi dini fungsi ginjal dapat bermanfaat dalam upaya pencarian target terapi yang lebih tepat, salah satunya melalui pendekatan metabolomik. Tujuan penelitian ini yaitu melihat perbedaan profil metabolit serum pasien DMT2 risiko rendah (n=16) dan tinggi (n=16) PGD berdasarkan klasifikasi KDIGO 2022 yang mengonsumsi metformin-glimepirid. Desain penelitian cross-sectional dengan teknik consecutive sampling dilakukan di Puskesmas Kecamatan Pasar Minggu dan RSUD Jatipadang. Sebanyak total 32 partisipan yang memenuhi kriteria inklusi dibandingkan profil metabolitnya berdasarkan kategori risiko PGD. Sampel darah, urin, serta data karakteristik dasar dan klinis dikumpulkan untuk analisis metabolomik. Analisis untargeted metabolomics dilakukan menggunakan LC/MS-QTOF dengan metode yang sudah tervalidasi. Pengolahan data dilakukan menggunakan MetaboAnalyst 5.0 dan SPSS versi 24.0. Seluruh metabolit yang terdeteksi diidentifikasi oleh database Metlin, HMDB, PubChem, dan KEGG. Tidak terdapat perbedaan bermakna pada seluruh karakteristik dasar dan klinis subjek penelitian. Terdapat perbedaan bermakna pada ekspresi metabolit antara dua kelompok sampel. Berdasarkan parameter VIP score >1; FC >1.2; p-value <0,05; AUC >0,65 yang ditetapkan, diperoleh tiga metabolit yang memiliki potensi sebagai senyawa biomarker dalam perkembangan PGD, yaitu acetyl-N-formyl-5-methoxykynurenamine (AFMK), phosphatydilinositol-4,5-bisphosphate (PIP2), dan cytidine diphosphate diacylglycerol (CDP-DAG). Berdasarkan ketiga metabolit tersebut, tiga jalur metabolisme berhasil terdeteksi dan berpotensi terlibat dalam perkembangan PGD yaitu metabolisme triptofan, metabolisme fosfatidilinositol, serta metabolisme gliserofosfolipid. 

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Type 2 diabetes mellitus (T2DM) is a metabolic disorder causing insulin regulation to be disrupted and may lead to diabetic kidney disease (DKD) complication. The current gold standard for assessing kidney function based on eGFR and albuminuria have some limitations. Therefore, a new method for assessing kidney function may be useful for a better therapeutic target discovery, such as through metabolomics approach. This study aims to compare the serum metabolite profiles of T2DM patients consuming metformin-glimepiride with low (n=16) and high (n=16) risk of DKD based on KDIGO 2022. A cross-sectional study with consecutive sampling method was carried out at Puskesmas Pasar Minggu and RSUD Jatipadang. A total of 32 participants fulfilled the inclusion criteria were compared for their metabolite profiles. Blood, urine, baseline and clinical characteristics data were collected to perform untargeted metabolomics analysis using a validated LC/MS-QTOF method. Data processing was performed using MetaboAnalyst 5.0 and SPSS 24.0. Metabolites were identified by Metlin, HMDB, PubChem, and KEGG databases. There were no significant differences among all basic and clinical characteristics of the participants. There were significant differences of metabolite expression between two sample groups. Based on the applied parameters VIP score >1; FC>1.2; p-value <0.05; AUC >0.65, three metabolites were found to have potential as biomarker in the development of DKD, namely acetyl-N-formyl-5-methoxykynurenamine (AFMK), phosphatydilinositol-4,5-bisphosphate (PIP2), and cytidine diphosphate diacylglycerol (CDP-DAG). Based on these metabolites, three metabolic pathways were detected and found to be potentially involved in the development of DKD, namely tryptophan metabolism, phosphatidylinositol metabolism, and glycerophospholipid metabolism."

"ABSTRAKPenyakit ginjal diabetik adalah suatu komplikasi yang disebabkan oleh diabetes melitus. Perkembangan penyakit ini mengarah kepada penyakit ginjal stadium akhir (ESRD) dan kardiovaskular yang meningkatkan morbiditas dan mortalitas pasien. Hal ini menunjukkan pentingnya manajemen terapi pada penyakit ginjal diabetik. Saat ini kontrol glikemik dan tekanan darah adalah manajemen utama pada penyakit ginjal diabetik. Walaupun demikian, diketahui beberapa pasien tetap mengalami progresivitas menjadi ESRD. Hal ini menunjukkan bahwa diperlukannya terapi baru untuk penyakit ginjal diabetik. Beberapa tahun terakhir telah dilakukan penelitian penelitian untuk menemukan target terapi baru yang berpotensi untuk terapi penyakit ginjal diabetik. Tulisan ini bertujuan untuk menelusuri, menelaah dan mensintesis hasil studi perkembangan terbaru untuk terapi penyakit ginjal diabetik pada golongan obat inhibitor sodium-glucose cotransporter 2 (SGLT2 inhibitor), agonis glucagon-like peptide-1 (GLP-1 agonist), antagonis endothelin-1 receptor (ET-1 antagonist) dan antagonis nonsteroidal mineralocorticoid receptor. Penelusuran literatur dilakukan dengan sistematik pada pusat data Pubmed, ScienceDirect, dan SpringerLink dan dipilah berdasarkan kriteria inklusi dan eksklusi yang ditetapkan. Efektivitas obat dievaluasi melalui kadar albuminuria dan estimasi laju filtrasi glomerulus. Berdasarkan hasil studi literatur 3 tahun terakhir, diperoleh hasil bahwa inhibitor SGLT2 dan agonis GLP 1 terbukti memiliki efek perlindungan ginjal dan kardiovaskular pada pasien diabetes melitus tipe 2. Kedua golongan tersebut juga dapat menurunkan tekanan darah dan berat badan. Studi saat ini juga menunjukkan antagonis ET 1 dan antagonis nonsteroidal mineralocorticoid receptor juga memiliki potensi sebagai terapi penyakit ginjal diabetik dikarenakan efeknya yang dapat mengurangi albuminuria pasien diabetes melitus tipe 2. Namun demikian untuk memastikan efikasi dan keamanan obat harus dilakukan uji klinis lebih lanjut.

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ABSTRACT

Diabetic kidney disease is a complication caused by diabetes mellitus. The development of the disease leads to end-stage renal disease (ESRD) and cardiovascular disease which increases patients morbidity and mortality. This show the importance of therapeutic management in diabetic kidney disease. Nowadays, glycemic control and blood pressure are the main management of diabetic kidney disease. However, it is known that some diabetes patients still progress to ESRD, highlighting the need to identify novel therapies for diabetic kidney disease. The last few years research has been carried out to find new therapeutic targets for therapy diabetic kidney disease. This article review aims explore, examine, and synthesize to new therapeutic studies for diabetic kidney disease in sodium glucose cotransporter 2 (SGLT2) inhibitor, glucagon-like peptide-1 (GLP-1) agonist, endothelin 1 receptor (ET-1) antagonist, dan nonsteroidal mineralocorticoid receptor antagonist. Literature searches were carried out systematically in Pubmed, ScienceDirect, and SpringerLink data centers and sorted according to inclusion and exclusion criteria. Efficacy of the drug was evaluated through the levels of albuminuria and estimated glomerular filtration rate (eGFR). Recent study showed that SGLT2 inhibitors and GLP 1 agonist have renal and cardiovascular protective effects in patient with type 2 diabetes mellitus. Both groups can also reduced blood pressure and body weight. Current studies show that ET-1 antagonists and nonsteroidal mineralocorticoid receptor antagonists also have the potential to treat diabetic kidney disease because of their effect on reducing albuminuria in patient with type 2 diabetes mellitus. However, to ensure efficacy and safety of the drug further clinical trials must be carried out."

"Background: Diabetic kidney disease (DKD), as a common cause of end-stage renal disease (ESRD), is a chronic complication of diabetes mellitus (DM). It has been established that vitamin D deficiency is one of DKD risk factors, which may be related to vitamin D receptor (VDR) polymorphisms. This study aimed to analyze the association between VDR polymorphisms and DKD in Indonesian population, also risk factors that influence it. Methods: a cross-sectional study was conducted in Type 2 DM patients who visited internal medicine outpatient clinic at Dr. Cipto Mangunkusumo Hospital, Jakarta, from November 2014 until March 2015. Data collection includes characteristics of subjects and laboratory examination, including BsmI polymorphisms in the vitamin D receptor gene. Patients with acute and severe disease were excluded from the study. Bivariate and multivariate analyses were done. Results: of 93 DM subjects, 42 (45.2%) subjects were without DKD and 51 (54.8%) subjects had DKD. Most of the subjects had the Bb genotype (89.2%), with no subject having the BB genotype. The proportions of the B and b alleles were 44.6% and 55.4%, respectively. There is no association between BsmI polymorphisms in the vitamin D receptor gene and DKD (OR = 1.243; CI 95% 0.334-4.621; p value = 0.751). Conclusion: the profile of BsmI polymorphisms in the vitamin D receptor gene in the Indonesian population were genotypes Bb (89.2%) and bb (10.8%). There was no association between BsmI polymorphisms in the vitamin D receptor gene and DKD. Duration of DM more than five years influenced the association between those variables."

"Penyakit Ginjal Diabetes (PGD) merupakan salah satu komplikasi mikrovaskular dari penyakit Diabetes Melitus Tipe 2 (DMT2) yang cenderung tidak terdeteksi secara dini sehingga diperlukan biomarker yang lebih efektif untuk mendeteksi penyakit ini. Tingginya HbA1c diketahui berpengaruh pada progresivitas PGD karena berkaitan dengan penurunan laju filtrasi glomerulus (eGFR) dan peningkatan rasio albumin kreatinin urin (UACR). Penelitian ini merupakan studi metabolomik tidak tertarget dan bertujuan untuk membandingkan metabolit urin pasien DMT2 risiko PGD rendah dengan HbA1c terkontrol dan tidak terkontrol pada pasien yang mengonsumsi terapi metformin-glimepirid. Penelitian dilakukan dengan desain potong lintang dengan teknik pengambilan sampel non-probabilitas di Puskesmas Kecamatan Pasar Minggu. Sebanyak 32 sampel dibagi menjadi dua kelompok, yakni kelompok HbA1c terkontrol (n=16) dan kelompok HbA1c tidak terkontrol (n=16). Sampel darah diambil untuk pengukuran HbA1c dan eGFR sedangkan sampel urin diambil untuk pengukuran UACR dan dianalisis metabolitnya. Analisis metabolit dilakukan menggunakan LC/MS-QTOF dan diolah datanya menggunakan MetaboAnalyst 6.0 serta berbagai database. Signifikansi metabolit antarkelompok diseleksi dengan parameter VIP>1, log2(FC)>1,2, dan p-value<0,05. Tiga metabolit yang berpotensi menjadi biomarker (AUC>0,65), yaitu oxaloacetate, 5'-phosphoribosyl-N-formylglycinamidine, dan (S)-dihydroorotate. Berdasarkan ketiga metabolit tersebut, jalur metabolisme yang terlibat meliputi (1) alanin, aspartat, dan glutamat, (2) asam sitrat (siklus Krebs), (3) glukoneogenesis, (4) piruvat, (5) pirimidin, dan (6) purin.

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Diabetic Kidney Disease (DKD) is one of the microvascular complications of Type 2 Diabetes Mellitus (T2DM) which tended not to be detected early, necessitating more effective biomarkers for its detection. Uncontrolled HbA1c was significantly associated with the progression of DKD because it is associated with a decrease in glomerular filtration rate (eGFR) and an increase in the urine albumin creatinine ratio (UACR). This study was an untargeted metabolomics study and aimed to compare urine metabolites in low-risk DKD T2DM patients with controlled and uncontrolled HbA1c undergoing metformin-glimepiride therapy. Conducted with a cross-sectional design and non-probability sampling at Pasar Minggu District Health Center, 32 samples were split into controlled (n=16) and uncontrolled HbA1c groups (n=16). Blood samples were taken for measurement of HbA1c and eGFR, while urine samples were taken for measurement of UACR and analyzed for metabolites. Metabolite analysis was carried out using LC/MS-QTOF and the data were processed using MetaboAnalyst 6.0 and various databases. Significant metabolites were identified with VIP>1, log2(FC)>1.2, and p-value<0.05. Three metabolites, namely oxaloacetate, 5'-phosphoribosyl-N-formylglycinamidine, and (S)-dihydroorotate, emerged as potential biomarkers (AUC>0.65). The involved metabolic pathways included (1) alanine, aspartate, and glutamate, (2) citric acid (Krebs cycle), (3) gluconeogenesis, (4) pyruvate, (5) pyrimidine, and (6) purine."

"[ABSTRAK Diabetic Kidney Disease (DKD) pada Diabetes Melitus Tipe 2 (DMT2) merupakan komplikasi kronik yang dapat dicegah dan ditunda progresifitasnya dengan pengontrolan glikemik yang baik dan penatalaksanaan yang tepat dari komorbid lainnya. Pengontrolan glikemik menjadi tanggung jawab bersama antara multidisiplin profesi kesehatan di ruang rawat (dokter, perawat, dietisien, farmasis) dengan pasien (serta keluarga). Model Self care Orem sangat sesuai untuk diaplikasikan dan dikembangkan di ruangan pada asuhan keperawatan pasien dengan penyakit kronik. Pasien dapat bersinergi secara aktif sesuai kemampuannya dalam mencapai tujuan dari setiap intervensi keperawatan. Disamping itu pendekatan model self care Orem sesuai untuk mempersiapkan pasien dalam meningkatkan kemampuan self care untuk pasca rawat. Pelaksanaan praktek berbasis pembuktian, pengukuran suhu kaki dengan termometer infrared dapat menjadi perangkat tambahan untuk menilai adanya gejala inflamasi lokal sehingga upaya deteksi dini menjadi lebih komprehensif. Pelaksanaan kegiatan inovasi pemantauan dan pemeriksaan kesehatan mandiri pada pasien DM dapat meningkatkan upaya promosi kesehatan pada pasien DM.ABSTRACT Diabetic Kidney Disease (DKD) in Type 2 Diabetes Mellitus (T2DM) is a chronic complication that can be prevented and delayed its progresivity with a good glycemic control and appropriate treatments. Glycemic control is a shared responsibility between the multidisciplinary health professions in the ward (doctors, nurses, dietisien, pharmacists) and patients (and families). Orem?s Self care model is appropriate to be applied and developed in the acute care of patients with chronic diseases. Patients can actively work together within its capabilities in achieving the objectives of each nursing intervention. Besides, Orem?s self care model approach appropriate to prepare the patient to improve the ability of self care for post-hospitalization. Implementation of evidence-based practice, the measurement of foot temperature with an infrared thermometer may be enhancements to assess the presence of local inflammatory symptoms so that early detection efforts become more comprehensive. Implementation of innovation activity monitoring and self health assesment can improve health promotion efforts in diabetic patients. ;Diabetic Kidney Disease (DKD) in Type 2 Diabetes Mellitus (T2DM) is a chronic complication that can be prevented and delayed its progresivity with a good glycemic control and appropriate treatments. Glycemic control is a shared responsibility between the multidisciplinary health professions in the ward (doctors, nurses, dietisien, pharmacists) and patients (and families). Orem?s Self care model is appropriate to be applied and developed in the acute care of patients with chronic diseases. Patients can actively work together within its capabilities in achieving the objectives of each nursing intervention. Besides, Orem?s self care model approach appropriate to prepare the patient to improve the ability of self care for post-hospitalization. Implementation of evidence-based practice, the measurement of foot temperature with an infrared thermometer may be enhancements to assess the presence of local inflammatory symptoms so that early detection efforts become more comprehensive. Implementation of innovation activity monitoring and self health assesment can improve health promotion efforts in diabetic patients. , Diabetic Kidney Disease (DKD) in Type 2 Diabetes Mellitus (T2DM) is a chronic complication that can be prevented and delayed its progresivity with a good glycemic control and appropriate treatments. Glycemic control is a shared responsibility between the multidisciplinary health professions in the ward (doctors, nurses, dietisien, pharmacists) and patients (and families). Orem’s Self care model is appropriate to be applied and developed in the acute care of patients with chronic diseases. Patients can actively work together within its capabilities in achieving the objectives of each nursing intervention. Besides, Orem’s self care model approach appropriate to prepare the patient to improve the ability of self care for post-hospitalization. Implementation of evidence-based practice, the measurement of foot temperature with an infrared thermometer may be enhancements to assess the presence of local inflammatory symptoms so that early detection efforts become more comprehensive. Implementation of innovation activity monitoring and self health assesment can improve health promotion efforts in diabetic patients. ]"