DAFTAR ISI

Halaman
JUDUL......................................................................................................................i
LEMBAR PERSETUJUAN....................................................................................ii
DAFTAR ISI...........................................................................................................iii
DAFTAR TABEL....................................................................................................v
DAFTAR GAMBAR..............................................................................................vi
DAFTAR SINGKATAN.......................................................................................vii
DAFTAR LAMPIRAN..........................................................................................xi
BAB I PENDAHULUAN
1.1 Latar Belakang .........................................................................................1
1.2 Rumusan Masalah ....................................................................................6
1.3 Tujuan Penelitian .....................................................................................7
1.4 Manfaat Penelitian ...................................................................................7
1.4.1 Manfaat ilmiah ..........................................................................7
1.4.2 Manfaat praktis .........................................................................7
BAB II KAJIAN PUSTAKA
2.1 Diabetes Melitus ...................................................................................8
2.2 Nyeri Neuropati Diabetik....................................................................11
2.2.1 Definisi dan Prevalensi Nyeri Neuropati Diabetik ......................11
2.2.2 Gejala Klinis dan Klasifikasi Nyeri Neuropati Diabetik..............13
2.2.3 Diagnosis Nyeri Neuropati Diabetik ...........................................15
2.2.4 Patofisiologi Nyeri Neuropati Diabetik .......................................17
2.2.5 Faktor Risiko Nyeri Neuropati Diabetik......................................25
2.3 Serotonin ................................................................................................28
BAB III
KERANGKA BERPIKIR, KONSEP, DAN HIPOTESIS PENELITIAN
3.1 Kerangka Berpikir Penelitian.................................................................38
3.2 Konsep Penelitian...................................................................................40
3.3 Hipotesis Penelitian................................................................................41

iii
BAB IV
METODE PENELITIAN
4.1 Tempat dan Waktu Penelitian.................................................................42
4.1.1 Tempat Penelitian.......................................................................42
4.1.2 Waktu Penelitian........................................................................42
4.2 Rancangan Penelitian .............................................................................42
4.3 Populasi dan Sampel...............................................................................43
4.3.1 Populasi......................................................................................43
4.3.2 Kriteria Inklusi Kasus.................................................................44
4.3.3 Kriteria Inklusi Kontrol..............................................................44
4.3.4 Kriteria Eksklusi Kasus dan Kontrol..........................................44
4.4 Besar Sampel..........................................................................................45
4.5 Teknik Penentuan Sampel......................................................................46
4.6 Variabel Penelitian..................................................................................47
4.6.1 Identifikasi Dan Klasifikasi Variabel.........................................47
4.6.2 Definisi Operasional Variabel....................................................47
4.7 Prosedur Penelitian.................................................................................52
4.7.1 Persiapan....................................................................................52
4.7.2 Alat Pengumpulan Data.............................................................52
4.7.3 Alur Penelitian............................................................................53
4.8 Analisis Data...........................................................................................54
DAFTAR PUSTAKA............................................................................................55
LAMPIRAN...........................................................................................................61

xi
 DAFTAR TABEL

Tabel 2.1 Klasifikasi Etiologi DM.............................................................................................9

Tabel 2.2 Kriteria Diagnosis DM.............................................................................................10

Tabel 2.3 Kadar Laboratorium Darah Untuk Diagnosis Diabetes dan Prediabetes.................11

xi
 DAFTAR GAMBAR

Gambar 2.1 Jalur Polyol...........................................................................................................19

Gambar 2.2 Efek Advanced Glycation End Products Pada Tubuh..........................................22

Gambar 2.3 Mekanisme Nyeri Neuropati Diabetik Dibandingkan Nyeri Nosiseptif..............25

Gambar 2.4 Patogenesis Neuropati Diabetik...........................................................................27

Gambar 2.5 Biogenesis dan Metabolisme Serotonin...............................................................29

Gambar 2.6 Mekanisme Substrat, Enzim Transporter Serotonin.............................................30

Gambar 2.7 Pengaruh Makanan Pada Serotonin dan Dopamin...............................................32

Gambar 2.8 Mekanisme 5-HT Dari Sel Enterokromafin Yang Berlokasi Pada Lumen Ileum33

Gambar 3.1 Bagan Kerangka Berpikir Penelitian....................................................................39

Gambar 3.2 Konsep Penelitian.................................................................................................40

Gambar 4.1 Bagan Rancangan Penelitian Kasus-Kontrol........................................................43

Gambar 4.2 Bagan Alur Penelitian...........................................................................................53

xi
 DAFTAR SINGKATAN

DM : Diabetes Melitus

ND : Neuropati Diabetes

NND : Nyeri Neuropati Diabetik

TCA : Tricyclic Antidepresant

SNRIs : Serotonin And Norepinephrine Re-Uptake Inhibitors

SSRI : Selective Serotonin Re-Uptake Inhibitor

WHO : World Health Organization

Riskesdas : Riset Kesehatan Dasar

TGT : Toleransi Glukosa Terganggu

GDP : Gula Darah Puasa

RSCM : Rumah Sakit Cipto Mangunkusumo

IASP : International Association for the Study of Pain

ADP : Adenosin difosfat

PARP : Poli ADP-ribose polimerase

AGEs : Advanced glycation end products

NMDA : N-methyl-D aspartate

HIV : Human Immunodeficiency Virus

AIDS : Acquired Immune Deficiency Syndrome

MH : Morbus Hansen

PERKENI : Perkumpulan Endokrinologi Indonesia

FFA : Free fatty acid

GLP-1 : Glucagon-like polypeptide-1

GIP : Glucose-dependent insulinotrophic polypeptide

xi
DPP-4 : Dipeptidyl peptidase IV

HGP : Hepatic glucose production

SGLT-2 : Sodium glucose co-transporter-2

SGLT-1 : Sodium glucose co-transporter-1

TTGO : Tes Toleransi Glukosa Oral

HbA1C : Hemoglobin A1C

HPLC : High-Performance Liquid Chromatography

NGSP : National Glycohaemoglobin Standarization Program

KAD : Ketoasidosis diabetik

SHH : Status hiperglikemi hiperosmolar

AAN : American Academy of Neurology

AAEM : American Association of Electrodiagnostic Medicine

AAPM & R : American Academy of Physical Medicine and Rehabilitation

DSPN : Dependent sensorimotor polyneuropathy

SFN : Small fiber neuropathy

QST : Quantitative sensory testing

CIDP : Chronic inflammatory demyelinating polyneuropathy (),

cAFT : Cardiovascular autonomic function

EMG : Electromyography

BPI-PDN : Brief pain inventory for painful diabetic neuropathy

ENMG : Electroneuromyography

PKC : Protein kinase C

NDP : Neuropati diabetik perifer

ROS : Rreactive oxygen species

NO : Nitric oxide

xi
Na+-K+-ATP-ase : Natrium-kalium-ATPase

Na+ : Natrium

NADPH : Nicotonamide adenine dinucleotide phosphate hydride

NOS : Nitric oxide synthase

NGF : Nerve growth factor

CGRP : Calcitonin-gen-regulated peptide

ATP : Adenosin triphosphate

RAGE : Receptor advanced glycation end products (

GABA : γ aminobutiric acid

TNF-α : Tumor Necrosis Factor Alpha

5-HT : 5 hydroxytryptamine

BDNF : Brain derived neurotrophic factor

SLE : Systemic lupus erythematosus

IMT : Indeks massa tubuh

DRG : Dorsal root ganglion

THP : Tryptofan hydrokxylase

AADC : Aromatic amino acid decarboxylase

MAT : Monoamine transporter

SERTs : Serotonin transporters

e5-HT : Extracellular serotonin release

MAO : Monoamine oxidase

ALDH : Aldehyde dehydrogenase

5-HIAA : 5-Hydroksyindoleacetic acid

DRN : Dorsal raphe nucleus

MRN : Median raphe nuclei

xi
mRNA : Messenger RNA

RVM : Rostral ventromedial medulo

TBC : Tuberkulosis

CTS : Carpal tunnel syndrome

CRS : Cervical Root Syndrome

PAD : Peripheral Arterial Disease

DN4 : Douleur Neuropathique 4

xi
 DAFTAR LAMPIRAN

Lampiran 1 Informasi Pasien...................................................................................................61

Formulir Persetujuan Tertulis...................................................................................................62

Lampiran 2 Lembar Pengumpulan Data..................................................................................63

Lampiran 3. Kuesioner DN4....................................................................................................65

Lampiran 4. Kuesioner Geriatric Depression Scale (GDS).....................................................66

xi