karya tulis akhir pengaruh pemberian kopi … · dan jumlah penurunan kadar glukosa darah tikus...
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KARYA TULIS AKHIR
PENGARUH PEMBERIAN KOPI TERHADAP PENURUNAN
KADAR GLUKOSA DARAH PADA TIKUS PUTIH STRAIN WISTAR
DIABETES MELLITUS TIPE 2
Oleh :
ALIFANETA YUSTISIANI
08020114
UNIVERSITAS MUHAMMADIYAH MALANG
FAKULTAS KEDOKTERAN
2012
PENGARUH PEMBERIAN KOPI TERHADAP PENURUNAN
KADAR GLUKOSA DARAH PADA TIKUS PUTIH STRAIN WISTAR
DIABETES MELLITUS TIPE 2
KARYA TULIS AKHIR
Diajukan kepada
Universitas Muhammadiyah Malang
untuk Memenuhi Salah Satu Persyaratan
dalam Menyelesaikan Program Sarjana
Fakultas Kedokteran
Oleh:
ALIFANETA YUSTISIANI
08020114
UNIVERSITAS MUHAMMADIYAH MALANG
FAKULTAS KEDOKTERAN
2012
LEMBAR PENGESAHAAN
LAPORAN HASIL PENELITIAN
Telah disetujui sebagai hasil penelitian
untuk memenuhi persyaratan
Pendidikan Sarjana Fakultas Kedokteran
Universitas Muhammadiyah Malang
Tanggal : 21 Maret 2012
Pembimbing I
dr. Isbandiyah, Sp.PD.
Pembimbing II
dr. Thontowi Djauhari, M.Kes
Mengetahui,
Fakultas Kedokteran
Dekan,
dr. Irma Suswati, M.Kes.
LEMBAR PENGUJIAN
Karya Tulis Akhir oleh Alifaneta Yustisiani
telah diuji dan dipertahankan di depan Tim Penguji
Pada tanggal : 21 Maret 2012
Tim Penguji
dr. Isbandiyah, Sp.PD. , Ketua
dr. Thontowi Djauhari, M.Kes. , Anggota
dr. Hawin Nurdiana, M.Kes. , Anggota
KATA PENGANTAR
Alhamdulillahirrabil’alamin, puji syukur kehadirat Allah SWT yang telah
melimpahkan karunianya sehingga penulis dapat menyelesaikan karya tulis akhir
yang berjudul “Pengaruh Pemberian Kopi Terhadap Penurunan Kadar Glukosa
Darah Pada Tikus Putih Strain Wistar Diabetes Mellitus Tipe 2”. Penulisan
penelitian ini dilakukan dalam rangka memenuhi salah satu syarat untuk
mencapai gelar Sarjana Kedokteran Jurusan Pendidikan Dokter pada Fakultas
Kedokteran Universitas Muhammadiyah Malang.
Dalam menyelesaikan usulan penelitian ini, penulis banyak mendapatkan
bimbingan dan bantuan dari berbagai pihak. Oleh kerena itu dalam kesempatan
ini penulis mengucapkan terima kasih kepada :
1. dr. Irma Suswati, M.Kes, selaku Dekan Fakultas Kedokteran.
2. dr. Meddy Setiawan, Sp.PD, selaku Pembantu Dekan I Fakultas
Kedokteran.
3. dr. Fathiyah Safitri, M.Kes, selaku Pembantu Dekan II Fakultas
Kedokteran.
4. dr. Iwan Sis Indrawanto, Sp.KJ, selaku Pembantu Dekan III Fakultas
Kedokteran.
5. dr. Isbandiyah, Sp.PD, selaku pembimbing I yang telah meluangkan
waktunya untuk membimbing dan mengoreksi demi kesempurnaan
penelitian ini.
6. dr. Thontowi Djauhari, M.Kes, selaku pembimbing II yang telah
meluangkan waktunya untuk memberi informasi dalam berbagai hal serta
memberi semangat dalam menyelesaikan penelitian ini.
7. dr. Hawin Nurdiana, M.Kes, selaku penguji yang telah memberi tambahan
ilmu dan kritik demi kesempurnaan penelitian ini.
8. Mas Aris Sandi beserta staf Lab. Kimia UMM, terima kasih banyak atas
segala bantuan, dukungan dan ilmu yang telah diberikan.
9. Orang tua dan keluarga saya yang telah memberikan bantuan dukungan
material dan moral.
10. Ega Astari, mbak Sisca Desi Prastyaningtias dan Irna Farah Nadiansyah
yang telah menjadi teman diskusi yang baik dan memberi banyak
masukan serta dukungan dalam menyelesaikan penelitian ini.
11. Sahabat-sahabat yang telah banyak membantu dan memberikan semangat
dalam menyelesaikan penelitian ini Dewi, Mega, Utari, Annisa, Fajar,
Afif, Dicky, Rezky.
12. Teman-teman angkatan 2008 Fakultas Kedokteran UMM, terima kasih
atas dukungan dan do’a sehingga dapat menyelesaikan tugas akhir ini.
13. Seluruh staf Tata Usaha FK UMM (Pak Yono, Bu Rom, Mas Didit, dan
Mas Faisal). Terima kasih atas bantuannya selama ini.
14. Mas Joko, mbak Tia, mbak Fat, mas Miftah, mbak Emi, mbak Dila dan
seluruh staf Lab. Terpadu FK UMM, terima kasih banyak atas bantuan
dan dukungannya.
Penulis menyadari bahwa penelitian ini masih belum sempurna, untuk itu
kritik dan saran kami harapkan demi kesempurnaan, serta kami mengharapkan
agar usulan penelitian ini dapat berguna bagi kita semua, serta bermanfaat untuk
bidang kedokteran.
Malang, Maret 2012
Penulis
ABSTRAK
Yustisiani, Alifaneta. 2012. Pengaruh Pemberian Kopi Terhadap Penurunan
Kadar Glukosa Darah Pada Tikus Putih Strain Wistar Diabetes Mellitus
Tipe 2. Tugas Akhir, Fakultas Kedokteran, Universitas Muhammadiyah
Malang. Pembimbing: (1) Isbandiyah (2) Thontowi Djauhari
Pendahuluan : Kopi merupakan salah satu minuman kegemaran masyarakat
dunia yang mengandung banyak senyawa antioksidan. Berbagai penelitian
membuktikan bahwa kopi dapat menurunkan risiko diabetes mellitus tipe 2.
Penelitian mengenai kopi sebagai terapi alternatif diabetes tipe 2 dengan melihat
kadar glukosa darah pada tikus putih strain wistar diabetes mellitus tipe 2 belum
pernah dilakukan di Indonesia.
Tujuan : Membuktikan pengaruh kopi terhadap penurunan kadar glukosa darah
pada tikus putih strain wistar diabetes mellitus tipe 2.
Metode : Eksperimen laboratoris rancangan the post test only control group
desain. Sampel tikus putih strain wistar dibagi 4 kelompok. Sampel I : kontrol
negatif, II: kontrol positif, dua kelompok lainnya diberikan kopi Robusta berbagai
dosis (5,4 mL/200 gr BB/ hari, 10,8 mL/200 gr BB/hari). Analisis data
menggunakan One Way Anova, uji Tukey 5%, uji korelasi dan uji regresi linier.
Hasil : Hasil uji One Way Anova terdapat pengaruh perlakuan dengan perbedaan
yang bermakna terhadap penurunan kadar glukosa darah. Dari uji korelasi
terdapat korelasi yang berbanding lurus dan sangat bermakna antara dosis kopi
dan jumlah penurunan kadar glukosa darah tikus putih diabetes mellitus tipe 2
dengan nilai Pearson Correlation -0,978 pada glukosa darah puasa dan -0,932
pada glukosa darah 2 jam post pandrial, sedangkan hasil uji regresi didapatkan
nilai R2 = 0,956 pada glukosa darah puasa dan 0,869 pada glukosa darah 2 jam
post pandrial.
Kesimpulan : Pemberian kopi berbagai dosis dapat menurunkan kadar glukosa
darah tikus diabetes mellitus tipe 2.
Kata kunci : diabetes mellitus tipe 2, kadar glukosa darah, kopi Robusta
ABSTRACT
Yustisiani, Alifaneta. 2012. The Influence of Coffee to Decrease the Blood
Glucose Level of Diabetes Type 2 Wistar Strain White Mice Models.
Final Assignment, Medical Faculty, University of Muhammadiyah
Malang, Adviser: (1) Isbandiyah (2) Thontowi Djauhari
Introduction : Coffee is one of several favorite drink in the world that contains
many antioxidant compounds. Various experiments prove that coffee can reduce
the risk of diabetes type 2. Study about coffee as the alternative therapies in
diabetes type 2 by observing the number of blood glucose level of of diabetes
type 2 wistar strain white mice models is not yet been conducted in Indonesia..
Objective : Understanding the effect of coffee to decrease the blood glucose level
in diabetes mellitus type 2 wistar strain white mice models.
Method : Laboratory experiment the post test only control group design. Wistar
white mice groups were divided into 4 groups. Sample I : negative control, II:
positive control, the other two groups were treated with Robusta coffee in various
doses (5,4 mL/200 grBW/day, 10,8 mL/200 gr BW/day). Data analysis used One
Way Anova, Tukey test 5%, correlation test, and linear regression test.
Result : One way Anova test result’s that there were an influence of treatments
with the obviously different to decrease the blood glucose level. From the
correlation test result that there were an inversely and meaningful correlation
between coffee doses and the increasing of decrease of blood glucose level in
diabetes mellitus type 2 white mice models with the value of Pearson Correlation
-0,978 fasting glucose blood and -0,932 2 hours post pandrial, while regression
test result was R2 = 0,956 fasting glucose blood and R
2= 0,869 2 hours post
pandrial.
Conclusion : Coffee administration in various doses can reduce the number of
blood glucose level in diabetes type 2 mice models.
Keywords : diabetes type 2, the number of blood glucose level, Robusta coffee
DAFTAR ISI
Halaman
HALAMAN JUDUL. ....................................................................................... i
LEMBAR PENGESAHAN ............................................................................. iii
LEMBAR PENGUJIAN .................................................................................. iv
KATA PENGANTAR ..................................................................................... v
ABSTRAK..... .................................................................................................. vii
ABSTRACT... .................................................................................................. viii
DAFTAR ISI .................................................................................................... ix
DAFTAR TABEL ............................................................................................ xiii
DAFTAR GAMBAR ....................................................................................... xiv
DAFTAR SINGKATAN ................................................................................. xv
DAFTAR LAMPIRAN .................................................................................... xvi
BAB 1 PENDAHULUAN .............................................................................. 1
1.1 Latar Belakang ............................................................................ 1
1.2 Rumusan Masalah ....................................................................... 3
1.3 Tujuan Penelitian ........................................................................ 4
1.3.1 Tujuan umum ..................................................................... 4
1.3.2 Tujuan khusus .................................................................... 4
1.4 Manfaat Penelitian ...................................................................... 4
1.4.1 Manfaat Akademik ............................................................ 4
1.4.2 Manfaat Klinis ................................................................... 4
1.4.3 Manfaat Masarakat ........................................................... 4
BAB 2 TINJAUAN PUSTAKA ..................................................................... 5
2.1 Kopi ............................................................................................. 5
2.1.1 Kopi Robusta ................................................................... 5
2.1.1.1 Definisi Kopi Robusta ..................................................... 5
2.1.1.2 Kandungan Kopi Robusta ............................................... 6
2.1.1.3 Manfaat Kopi Robusta. ................................................... 6
2.2 Diabetes Mellitus ......................................................................... 11
2.2.1 Definisi Diabetes Mellitus ................................................. 11
2.2.2 Diabetes Mellitus Tipe II ................................................... 11
2.2.3 Patogenesis Diabetes Mellitus Tipe II................................ 13
2.2.4 Manifestasi klinis ............................................................... 14
2.2.5 Diagnosis Diabetes Mellitus .............................................. 15
2.2.6 Pengaturan Glukosa Darah ................................................. 16
2.2.6.1 Glikolisis. ........................................................................ 17
2.2.6.2 Glukoneogenesis. ............................................................ 18
2.2.7 Mekanisme Homeostasis Glukosa Darah .......................... 19
2.3 Kopi dan Diabetes Mellitus Tipe 2 .............................................. 22
2.3.1 Kafein.. ............................................................................... 22
2.3.2 Chlorogenic Acid. .............................................................. 23
2.4 Bahan Penginduksi Diabetes Mellitus ......................................... 25
2.4.1 Streptozotocin .................................................................... 25
2.4.2 Nicotinamide ...................................................................... 29
BAB 3 KERANGKA KONSEP DAN HIPOTESIS....................................... 22
3.1 Kerangka Konsep ........................................................................ 32
3.2 Hipotesis ...................................................................................... 35
BAB 4 METODE PENELITIAN ................................................................... 36
4.1 Rancangan Penelitian ................................................................. 36
4.2 Lokasi .......................................................................................... 36
4.3 Populasi dan Sample
4.3.1 Populasi .............................................................................. 36
4.3.2 Sampel Penelitian ............................................................... 36
4.3.3 Estimasi Besar Sampel ....................................................... 36
4.3.4 Karakteristik Sampel Penelitian . ....................................... 37
4.4 Variabel Penelitian ...................................................................... 38
4.4.1 Variabel Bebas ................................................................... 38
4.4.2 Variabel Terkait ................................................................. 38
4.4.3 Variabel Kontrol................................................................. 38
4.4.4 Definisi Operasional........................................................... 38
4.5 Alat dan Bahan. ........................................................................... 39
4.5.1 Alat ..................................................................................... 39
4.5.2 Bahan.................................................................................. 40
4.6 Alur Penelitian ............................................................................ 41
4.7 Prosedur Penelitian...................................................................... 42
4.7.1 Adaptasi Hewan Uji ........................................................... 42
4.7.2 Penentuan Dosis ................................................................. 42
4.7.3 Penyiapan Larutan Uji........................................................ 43
4.7.4 Pengambilan Darah Tikus. ................................................. 44
4.7.5 Percobaan ........................................................................... .44
4.8 Analisis Data ............................................................................... 48
BAB 5 HASIL PENELITIAN DAN ANALISIS DATA. .............................. 49
5.1 Hasil Penelitian. ........................................................................... 49
5.2 Analisis Data ............................................................................... 52
5.2.1 Uji One Way ANOVA ...................................................... 52
5.2.2 Hasil Uji Tukey 5% ........................................................... 53
5.2.3 Uji Korelasi ........................................................................ 54
5.2.4 Uji Regresi ......................................................................... 55
BAB 6 PEMBAHASAN ................................................................................. 58
BAB 7 KESIMPULAN DAN SARAN .......................................................... 63
7.1 Kesimpulan .................................................................................. 63
7.2 Saran ............................................................................................ 63
DAFTAR PUSTAKA ...................................................................................... 64
LAMPIRAN .................................................................................................... 69
DAFTAR TABEL
Tabel 2.1 Komposisi Kimia Biji Kopi Robusta yang Disangrai ..................... 6
Tabel 2.2 Kadar Glukosa Darah Sewaktu dan Puasa Sebagai Patokan
Penyaring dan Diagnosis Diabetes Mellitus ..................................... 15
Tabel 2.3 Glucose Transporters ....................................................................... 21
Tabel 4.1 Konversi Dosis Antar Spesies .......................................................... 43
Tabel 5.1 Hasil Rerata Kadar Glukosa Darah Tikus ........................................ 50
Tabel 5.2.1 Resume Uji Tukey ........................................................................ 54
Tabel 5.2.2 Uji Korelasi Kadar Glukosa Darah Puasa Tikus Setelah Pemberian
Kopi...................................................................................54
Tabel 5.2.3 Uji Korelasi Kadar Glukosa Darah 2 Jam PP Tikus Setelah
Pemberian Kopi....................................................................55
DAFTAR GAMBAR
Gambar 2.1 Struktir Kimia Streptozotocin ..................................................... 26
Gambar 2.2 Struktir Kimia Nicotinamide ....................................................... 29
Gambar 2.3 Skema Mekanisme Streptozotocin dan Nicotinamide ................. 31
Gambar 3.1 Kerangka Konseptual .................................................................. 32
Gambar 4.1 Alur Penelitian............................................................................. 41
Gambar 5.1 Diagram Batang Rerata Hasil Pengukuran Kadar Glukosa Darah
Pasca Perlakuan 1 ........................................................................ 51
Gambar 5.2 Diagram Batang Rerata Hasil Pengukuran Kadar Glukosa Darah
Pasca Perlakuan 2 ........................................................................ 52
Gambar 5.3 Uji Regresi Penurunan Kadar Glukosa Darah Puasa Tikus Setelah
Pemberian Kopi ........................................................................... 56
Gambar 5.4 Uji Regresi Penurunan Kadar Glukosa Darah 2 Jam PP Tikus
Setelah Pemberian Kopi .............................................................. 57
DAFTAR SINGKATAN
ADP : Adenosine Diphosphate
AMP : Adenosine Monophosphate
ANOVA : Analysis of Variance
ATP : Adenosine Triphosphate
cAMP : cyclic Adenosine Monophosphate
CGA : Chlorogenic acid
DM : Diabetes Melitus
DNA : Deoxyribose Nucleic Acid
eNOS : endothelial Nitric Oxide Synthase
GDM : Gestational Diabetes Mellitus
GLUT : Glucose Transporter
IDDM : Insulin Dependent Diabetes Mellitus
NAD : Nicotinamide Adenine Dinucleotide
NADH : Nicotinamide Adenine Dinucleotide Hydrogenase
NADP : Nicotinamide Adenine Dinucleotide Phosphate
NADPH :Nicotinamide Adenine Dinucleotide Phosphate Hydrogenase
NO : Nitric Oxide
NOD : Non-Obese Diabetes
PBS : Phosphate Buffered Saline
PJK : Penyakit Jantung Koroner
PP : Post Prandial
RNA : Ribo Nucleic Acid
ROS : Reactive Oxygen Species
SHBG : Sex Hormone Binding Globulin
STZ : Streptozotocin
WHO : World Healthy Organization
DAFTAR LAMPIRAN
Lampiran 1 Data Pengamatan Glukosa Darah ................................................ 69
Lampiran 2 Analisis Data Kadar Glukosa Darah ............................................ 73
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