Hubungan Antara Diabetes Melitus dan Genetik

Diabetes

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Pastikan kamu membaca artikel ini secara lengkap, karena di dalamnya akan diulas bermacam-macam hal mengenai diabetes. Semoga dengan membaca artikel ini, kamu dapat menemukan informasi yang berguna bagi kamu baik untuk memerangi diabetes ataupun mencegah terjadinya diabetes.

Pendahulan Singkat Mengenai Diabetes

Hipergilkemia adalah suatu kondisi medis berupa peningkatan kadar glukosa darah melebihi kadar normal yang menjadi karakteristik beberapa penyakit terutama diabetes melitus di samping berbagai kondisi lainnya. Diabetes Melitus (DM) saat ini menjadi salah satu ancaman kesehatan global. Berdasarkan penyebabnya, Diabetes Melitus dapat diklasifikasikan menjadi 4 kelompok, yaitu DM Tipe 1, DM Tipe 2, DM Gestasional, dan DM Tipe lainnya.

Berdasarkan data International Diabetes Federation (IDF) Atlas tahun 2019, jumlah penyandang diabetes melitus di dunia saat ini berkisar 463 juta, dan diperkirakan akan meningkat menjadi sekitar 700 juta di tahun 2045 mendatang. Organisasi Kesehatan Dunia (World Health Organization/WHO) memprediksi akan terjadi peningkatan jumlah pasien DM tipe 2 yang cukup besar pada tahun-tahun mendatang. Indonesia merupakan negara urutan ke-7 dari 10 negara dengan jumlah penyandang DM terbanyak di dunia, yaitu sekitar 10 juta penduduk. Riset Kesehatan Dasar (RISKESDAS) menyebutkan bahwa proporsi penyandang DM pada penduduk usia ≥15 tahun di Indonesia berdasarkan pemeriksaan darah adalah 5.7% pada tahun 2007, meningkat menjadi 6.9% pada tahun 2013, dan semakin meningkat menjadi 8.5% pada tahun 2018.

Sejalan dengan itu, Badan Pusat Statistik Indonesia tahun 2003, memperkirakan bahwa penduduk Indonesia yang berusia di atas 20 tahun sebanyak 133 juta jiwa, dengan prevalensi DM sebesar 14.7% pada daerah urban dan 7.2% pada daerah rural. Dengan pertambahan jumlah penduduk di tahun 2030 nanti, diperkirakan bahwa jumlah penderita DM di Indonesia juga akan meningkat.

Komplikasi yang terjadi akibat penyakit diabetes melitus dapat berupa gangguan pada pembuluh darah baik pada pembuluh darah besar ataupun pembuluh darah kecil, serta gangguan saraf. Gangguan seperti ini tidak hanya terjadi pada penderita DM tipe 2 yang sudah lama, tetapi dapat juga terjadi pada orang yang baru terdiagnosis DM tipe 2. Komplikasi pada pembuluh darah besar umumnya mengenai organ jantung, otak, dan pembuluh darah, sedangkan yang mengenai pembuluh darah kecil dapat mengganggu mata dan juga ginjal.

Diabetes Melitus

Diabetes Melitus (DM) mengacu pada sekelompok gangguan metabolik yang ditandai dengan adanya peningkatan kadar gula darah. Beberapa jenis DM disebabkan oleh adanya interaksi yang kompleks antara faktor genetik dan faktor lingkungan. Diagnosis DM ditegakkan atas dasar pemeriksaan kadar glukosa darah dan kadar HbA1C. Pemeriksaan glukosa darah yang dianjurkan adalah pemeriksaan glukosa yang sampelnya menggunakan darah dari pembuluh darah besar. Apabila kamu atau anggota keluargamu ada yang mengalami gejala seperti berikut, mungkin perlu dicurigai adanya DM dan sebaiknya segera diperiksakan ke dokter.

Berikut gejala/keluhan yang mungkin dialami, yaitu:

  • Keluhan klasik DM: sering buang air kecil (polyuria), cepat haus (polydipsia), banyak makan (polyphagia) dan penurunan berat badan yang tidak dapat dijelaskan sebabnya.
  • Keluhan lain: lemah badan, kesemutan, gatal, mata kabur, dan disfungsi ereksi pada pria, serta gatal pada bibir kelamin wanita.

Selain gejala/keluhan, berikut kriteria hasil pemeriksaan gula darah yang memenuhi diagnosis DM, sebagai berikut:

  • Pemeriksaan glukosa darah puasa ≥126 mg/dL. Dengan syarat puasa, yaitu kondisi tidak ada asupan kalori (baik dari makanan ataupun minuman) minimal 8 jam, ATAU
  • Pemeriksaan glukosa darah ≥200 mg/dL setelah 2 jam Tes Toleransi Glukosa Oral (TTGO) dengan beban glukosa 75 gram, ATAU
  • Pemeriksaan glukosa darah sewaktu ≥ 200 mg/dL dengan keluhan klasik, ATAU
  • Pemeriksaan HbA1C ≥ 6.5% dengan metode yang sudah terstandarisasi.

Kadang kala dari hasil pemeriksaan laboratorium, terdapat hasil pemeriksaan yang tidak memenuhi kriteria normal atau kriteria DM digolongkan ke dalam kelompok prediabetes yang meliputi toleransi toleransi glukosa terganggu (TGT) dan glukosa darah puasa terganggu (GDPT).

  • Glukosa Darah Puasa Terganggu (GDPT): Hasil pemeriksaan glukosa plasma puasa antara 100 – 125 mg/dL dan pemeriksaan TTGO glukosa darah 2 jam < 140 mg/dL.
  • Toleransi Glukosa Terganggu (TGT): Hasil pemeriksaan glukosa darah 2 jam setelah TTGO antara 140 – 199 mg/dL dan glukosa darah puasa < 100 mg/dL.
  • Selain itu, diagnosis prediabetes dapat juga ditegakkan berdasarkan hasil pemeriksaan HbA1C yang menunjukkan angka 5.7 – 6.4%.

 

Klasifikasi Diabetes Melitus

Secara umum, diabetes dapat dikelompokkan menjadi beberapa kategori, yaitu :

  1. Diabetes tipe 1; secara umum disebabkan oleh proses autoimun yang merusak sel β pankreas (yang secara normal berfungsi untuk mengeluarkan insulin); akibatnya jumlah insulin dalam tubuh akan berkurang.
  2. Diabetes tipe 2; secara umum disebabkan oleh resistensi insulin dalam tubuh seseorang sebagai akibat ketidakcukupan pengeluaran insulin.
  3. Diabetes Gestasional; DM yang terdiagnosis dalam kehamilan trimester dua atau tiga.
  4. Diabetes tipe lainnya.

Dua kelompok yang terbesar adalah DM tipe 1 dan DM tipe 2, sehingga tipe lainnya tidak akan dibahas dalam artikel ini.

DM tipe 1 dan 2 adalah penyakit heterogen di mana gejala / keluhan dan perjalanan penyakit sangatlah bervariasi. Paradigma tradisional yang beranggapan bahwa DM tipe 2 hanya terjadi pada orang dewasa dan DM tipe 1 hanya pada anak-anak sudah tidak akurat, karena kedua tipe DM ini dapat terjadi pada semua kelompok usia.

 

Diabetes Melitus Tipe 1

DM tipe 1

DM tipe 1 adalah hasil dari interaksi faktor genetik, lingkungan, serta imunologi yang berdampak akhir pada rusaknya sel β pankreas. DM tipe 1 dapat terjadi pada semua usia, tetapi paling sering terjadi sebelum usia 20 tahun. Kerentanan terhadap timbulnya DM tipe 1 melibatkan banyak gen. Gen mayor yang berperan untuk DM tipe 1 terletak pada regio HLA kromosom nomor 6. Polimorfisme/variasi genetik pada regio HLA menyumbang sekitar 40-50% risiko genetik terjadinya DM tipe 1. Regio ini mengandung gen yang bertanggung jawab dalam proses imunologis dalam tubuh. Mayoritas individu dengan DM tipe 1 mempunyai turunan HLA DR3 dan/atau DR4 yang berasal dari salah satu orang tua (disebut juga haplotype). Dari hasil penelitian, jenis haplotype yang ditemukan adalah DQA1*0301, DQB1*0302, dan DQB1*0201 sangat berhubungan dengan kasus DM tipe 1. Menurut studi, turunan gen ini ditemukan pada 40% anak-anak dengan DM tipe 1 dibandingkan dengan 2% populasi normal di Amerika.

Selain regio HLA, telah ditemukan setidaknya 20 lokasi gen tambahan yang ikut berkontribusi terhadap terjadinya DM tipe 1 (misalnya : gen CTLA-4, Reseptor Interleukin 2, PTPN22, dan lain sebagainya). Meskipun begitu, ditemukan juga gen-gen yang berfungsi sebagai proteksi perlindungan munculnya DM tipe 1, yaitu : DQA1*0102 dan DQB1*0602 dimana gen-gen ini sangat jarang pada penderita DM tipe 1 (<1%).

Hingga saat ini, penelitian mengenai faktor genetik yang berperan dalam terjadinya DM tipe 1 masih berlanjut. Penelitan skala besar yang telah dilakukan selama ini telah banyak menemukan gen-gen yang berpengaruh terhadap terjadinya DM tipe 1. KIAA0350, UBASH3A, HLA-DQB1, CLEC16A, BACH2, dan masih banyak lagi gen-gen lain yang diperkirakan ikut berpengaruh terhadap terjadinya kasus DM tipe 1 pada usia muda.

Jika kamu adalah seorang laki-laki dengan DM tipe 1, kemungkinan anak kamu untuk menderita DM tipe 1 adalah 1/17, namun jika kamu adalah seorang wanita dengan DM tipe 1 dan kamu melahirkan seorang anak sebelum usia 25 tahun, maka risiko menjadi 1/25, namun jika anak kamu lahir setelah usia 25 tahun, risiko anak kamu mengalami DM tipe 1 adalah 1/100. Risiko anak kamu menjadi dua kali lipat jika kamu menderita diabetes sebelum usia 11 tahun. Bahkan jika kamu dan pasanganmu sama-sama menderita DM tipe 1, risiko anak kamu menderita DM tipe 1 adalah antara 1/10 dan 1/4.

Secara sederhana, faktor risiko genetik dan terjadinya kasus DM tipe 1 adalah sebagai berikut :

  • Ibu dengan diabetes akan meningkatkan risiko terjadinya diabetes sebanyak 2%.
  • Ayah dengan diabetes akan meningkatkan risiko terjadinya diabetes sebanyak 8%.
  • Kedua orang tua dengan diabetes akan meningkatkan risiko sebanyak 30%.
  • Kakak atau Adik dengan diabetes akan meningkatkan risiko sebanyak 10%.
  • Kembar tidak identik dengan diabetes akan meningkatkan risiko sebanyak 15%.
  • Kembar identik dengan diabetes akan meningkatkan risiko 40%.

 

Diabetes Melitus Tipe 2

DM Tipe 2

Resistensi insulin dan pengeluaran insulin yang tidak normal dari tubuh ada pusat penyebab terjadinya DM tipe 2. Meskipun penyebab terjadinya penyakit sudah jelas, namun masih banyak diskusi terkait faktor genetik yang berpengaruh, misalnya pada etnis Latin lebih banyak ditemukan kejadian resistensi insulin dan pada etnis Asia Timur dan Asia Selatan lebih banyak ditemukan gangguan fungsi sel β.

DM tipe 2 adalah sebuah penyakit yang dipengaruhi oleh banyak gen dan banyak faktor lainnya (kerentanan genetik, obesitas, nutrisi yang buruk, dan aktivitas fisik yang rendah). Anak-anak yang lahir dari ibu yang mengalami hiperglikemia selama kehamilan juga meningkatan risiko terjadinya DM tipe 2. Penelitian untuk memetakan gen dalam tubuh manusia yang sudah dimulai sejak lama masih terus dilakukan hingga saat ini, dan sudah menemukan >240 lokasi gen yang mungkin berhubungan dengan diabetes melitus tipe 2, meskipun begitu banyak gen yang telah diteliti gagal menunjukkan adanya hubungan yang kuat. Terdapat beberapa gen, seperti : ABCC8, KCNJ11, SLC2A2, HNF4A, serta INS menunjukkan adanya pengaruh antara aktivitas sel β dengan resistensi insulin. Masih banyak gen-gen lain yang turut memberikan kontribusi terganggunya aktivitas insulin dalam tubuh sehingga saat terjadi gangguan pada gen tersebut, akan meningkatkan risiko terjadinya DM tipe 2. Berikut contoh-contoh gen yang berpengaruh :

  • TBC1D4; dalam beberapa variasinya akan meningkatkan risiko terjadinya DM tipe 2 pada etnis tertentu.
  • ABCB11; ditemukan berpengaruh pada kadar glukosa puasa dalam studi pada individu dari Finlandia dan Sardinia.
  • MTNR1B; berhubungan dengan kejadian DM tipe 2, kadar glukosa puasa, dan aktivitas sel β pada populasi di Prancis.

Dengan semakin banyaknya penelitian genetik yang dilakukan, maka jenis gen yang akan berpengaruh akan semakin banyak ditemukan, namun risiko dari faktor genetik diperkirakan <10% menyebabkan penyakit ini.

Apabila di dalam keluarga Anda terdapat riwayat penderita DM tipe 2, akan sulit untuk menentukan apakah penyakit Anda disebabkan oleh pola hidup yang kurang baik atau akibat kelainan genetik atau bahkan kedua faktor ini bekerja sama. Kabar baiknya, penelitian menunjukkan bahwa kejadian DM tipe 2 dapat diperlambat atau dicegah dengan berolahraga, mengurangi berat badan, serta pola hidup yang baik.

Secara sederhana, faktor risiko genetik dan terjadinya kasus DM tipe 2 adalah sebagai berikut :

  • Jika Ibu atau Ayah mempunyai DM, maka risiko akan meningkat sebesar 15%.
  • Jika Ayah dan Ibu mempunyai DM, maka risiko akan meningkat sebesar 75%.
  • Jika kembar tidak identik mempunyai DM, maka risiko akan meningkat sebesar 10%.
  • Jika kembar identik mempunyai DM, maka risiko akan meningkat sebesar 90%.
Sumber :
  • Pedoman Pengelolaan dan Pencegahan Diabetes Melitus Tipe 2 di Indonesia 2021. Perkumpulan Endokrinologi Indonesia.
  • Pedoman Pemantauan Glukosa Darah Mandiri 2021. Perkumpulan Endokrinologi Indonesia.
  • Harrison’s Principle of Internal Medicine, 20th edition.
  • Standards of Care 2020. American Diabetes Association.
  • Sayed S, Nabi AHMN. Diabetes and Genetics: A Relationship Between Genetic Risk Alleles, Clinical Phenotypes and Therapeutic Approaches. Adv Exp Med Biol. 2021;1307:457-498. doi: 10.1007/5584_2020_518. PMID: 32314317.
  • https://diabetes.org/diabetes/genetics-diabetes
  • https://www.diabetes.co.uk/diabetes-and-genetics.html
dr. Yohanes Edwin J
dr. Yohanes Edwin Jonatan
Dokter Umum | + posts

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