Diabetes Mellitus.kuliah2013

7/27/2019 Diabetes Mellitus.kuliah2013

1/190

DIABETES MELLITUS

EPIDEMIOLOGI DANPERMASALAHANNYA

Dr. SUHAEMI, SpPD, FINASIM


2/190

Diabetes Mellitus

Suatu Sindroma kelainan metabolik,ditandai adanya hiperglikemia, akibat

defek sekresi insulin, defek kerjainsulin, atau kombinasi keduanya.


3/190

Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications. Department of Noncommunicable Disease Surveillance,

World Health Organization, Geneva 1999.

Definition of Type 2 Diabetes

Type 2 diabetes is characterised by:

chronic hyperglycaemia with disturbances ofcarbohydrate, fat and protein metabolism

defects in insulin secretion (-cell dysfunction)

and insulin action (insulin resistance)


4/190

Type 1 diabetes -cell destruction

Type 2 diabetes

Progressive insulin secretory defect

Other specific types of diabetes

Genetic defects in -cell function, insulin action

Diseases of the exocrine pancreas

Drug- or chemical-induced

Gestational diabetes mellitus

Classification of Diabetes

ADA. I. Classification and Diagnosis. Diabetes Care2011;34(suppl 1):S12.


5/190

Diabetes Mellitus :a group of diseases characterized by high levels of blood glucose resulting fromdefects in insulin production, insulin action, or both

20.8 million in US ( 7% of population)

estimated 14.6 million diagnosed (only 2/3)

Consists of 3 types:

1) Type 1 diabetes2) Type 2 diabetes

3) Gestational diabetes

Complications :- Stroke

- Heart attack

- Kidney disease

- Eye Disease

- Nerve Damage


6/190

Diabetes Mellitus

Type 1 Diabetes

- cells that produce insulin aredestroyed

- results in insulin dependence

- commonly detected before 30

Type 2 Diabetes

- blood glucose levels rise due

to

1) Lack of insulinproduction

2) Insufficient insulinaction (resistant cells)

- commonly detected after 40

- effects > 90%

- eventually leads to -cellfailure

(resulting in insulin dependence)

Gestational Diabetes3-5% of pregnant women in the US

develop gestational diabetes


7/190

Diabetes Mellitus Type 1

Results from inability ofislet cells to produceinsulin

Also known as insulin-dependent or juvenile-onset diabetes

Cause is unknown, but

likely to have genetic,autoimmune component


8/190

molcules HLA de

classe II (DR3-DR4)

virus

insuline

lymphocyteCD 4

Ag viraux

et de cell.

CD 8

IFNg

IL-2

NK

lymphocyteB

cytokines

anticorps

cell.

facteurs

denvironnement?


9/190

Diabetes Mellitus Type 2

Results from decreasedinsulin sensitivity anddecreased pancreatic

beta-cell function


10/190Adapted from International Diabetes Center (IDC). Minneapolis, Minnesota

Natural History of Type 2 Diabetes

0 10 20 30

Years of Diabetes

-cell

function

Plasmaglucose

Insulin resistance

Insulin secretion

Fasting glucose

Post-prandial

glucose

Insulin Rx

OADs

TLC

OADACEIAIIA


11/190

Gestational Diabetes

Diabetes that firstpresents during pregnancy

Occurs in 2-10% of

pregnancies 30-60% chance of

developing T2DM


12/190

RISKESDAS 2008

Diagnosed patients

Undiagnosed patients

Indonesian Basic Health

Research (RISKESDAS)

Total DM = 5,7%

Diagnosed DM = 1,5%

Undiagnosed DM = 4,2%

IGT = 10,2 %

DM patients estimated (WHO)

20002030

8 million >21

million


13/190

Epidemiology of Diabetes


14/190

Diabetes in the World

Viva la Vida con Salud!

millions

India

31.7

China

20.8

USA

17.7

Indonesia

8.4

Japan

6.8

Year2000

Reference: Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes. Diabetes Care. 2004; 27(5): 1047-1053.


15/190

Diabetes in the World

Viva la Vida con Salud!

millions

India

79.4

China

42.3

USA

30.3

Indonesia

21.3

Japan

8.9

Year2030

Reference: Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes. Diabetes Care. 2004; 27(5): 1047-1053.


16/190

Why is Diabetes on theIncrease?

Ethnicity and family history are implicated

Closely associated with overweight or obesepeople

Increased switch to Western diet and lifestyle

T Y P E 2 D I A B E T E S

Obesity

International Diabetes Federation. Diabetes Atlas, 2nd Edition, 2003

Western lifestyleGenetic component


17/190


18/190


19/190


20/190

MegaMeals


21/190

Super Size

Each 12 oz soda has 10tsp sugar (150 cal)

One can of soda/day childs risk obesity 60%

Most popular Canadiandrink

> 110 L/ person/yr

1942-1998:

US production increased9X


22/190


23/190


24/190


25/190


26/190


27/190


28/190

Diabetes

Presentation title in footer | 00 Month 0000

28

Children > 10 years

Metformin dose < 2000mg

Metformin Approved Use

Combined w i th Insul in

Single Therapy

POM Indon esia ; mon otherapi or comb inat ion with insul in ;

-Glucophage 1000 mg film-coated tablet can be used in children from 10 years of age and adolescents.-The maximum recommended dose of metformin hydrochloride is 2 g daily, taken as 2 or 3 divided doses.


29/190


30/190

Impact of DM

25.8 million Americans have diabetes (8.3%of population)

The number of Americans treated for

diabetes doubled from 1996 to 2007. 1 in 3 Americans born in 2000 will have

diabetes in their lifetime

Annual costs -- $132 billion

Leading cause of blindness, ESRD,amputations, MI, strokes


31/190

Resistensi

Insulin

Diabetes

Tipe 2

DeFronzo et al. Diabetes Care 1992;15:318-68

Diabetes Melitus

Definisi :

- gangguan metabolisme

- kenaikan kadar glukosa darah kronis

- disebabkan oleh adanya gangguan produksi insulin akibat kerusakan

sel beta pankreas dan atau kerja insulin.

Kerusakan sel

Beta pankreas


32/190


33/190


34/190

Types of diabetes

Copyright 2008 Dr. Salme Taagepera, All rights reserved.

1. Type 1 = autoimmune disease resulting in lossof insulin production

2. Type 2= associated with obesity, lack ofcellular response to insulin

Type 1Type 2


35/190

Physiology: Role of Insulin


36/190


37/190


38/190


39/190

H istory of DM

Diabetes

Greek for

passing water

like a siphon

Mellitus

Latin for

sweetened

with honey

Ebers Papyrus

(Egyptian, 1500 B.C.)

first depiction of diabetes mellitus

- urination of excess amounts

- manipulation of diet therapy


40/190

Sudah dikenal sejak zaman Ebers Papyrus 1550SM

Willis : mencatat ada rasa manis pada urine IBNU SINA : Gangren Diabetic Matthew Dobson : Rasa manis karena gula 1815 : Chevreul (ahli Kimia) membuktikan bahwa

gula dalam urine adalah glukosa 1921 : Frederic Grant Banting, Charles Best

berhasil mengekstraksi insulin pertama kali daripankreas anjing

11 Jan 1922 : Leonardo Thompson, remajamerupakan pasien pertama yang mendapat insulindi RS Toronto Kanada

1979 : Goedde menghasilkan human insulindengan rekayasa genetik


41/190

Faktor Resiko untuk Terjadinya DM

Kelompok Usia > 45 tahun

Gemuk : BB > 120% BBI (IMT > 27 kg/m2)

Hypertensi

Riwayat Keluarga DM Riwayat melahirkan bayi > 4 kg.

Riwayat DM pada waktu hamil (DM Gestasi)

Dislipidemia : HDL < 35 mg/dl, Trigliserida > 250mg/dl

Pernah mengalami gangguan toleransi glukosa


42/190

Etiologi

Herediter, diperlukan faktor lain yang disebutfaktor risiko atau faktor pencetus

Virus Pada DM tipe 1 dijumpai HLAgen yang rentan

terhadap infeksi virus tertentu. Virus yang selalu menimbulkan insulitis adalah :

Coxackie, Mumps, Rubella, Cytomegalovirus,Herpes, dll.

Obesitas Kadar Insulin cukup tetapi tidak efektif (Resistensi

Insulin )

Memakai obat-obatan yang menyebabkanKadar Gula Darah meningkat

Causes of Mortality in Diabetic


43/190

Not specified

Others

Tuberculosis

Accident / suicide

Gangrene

Renal insufficiency

Diabetic coma

Infections

Tumors

Stroke

Myocardial infarction

0 10 20 30 40

% deaths in diabetics3.4

11.4

0.9

2.1

2.7

2.9

3.1

6.7

10

22

34.7

Panzram G. Diabetologia 1987; 30: 120-31

Causes of Mortality in DiabeticPatients


44/190

Pankreas

Terletak dibelakang lambung

Berat : 200250 gram

Bentuk : Kerucut terbaring

Bagian yang lebar : Kepala (Caput)

Bagian yang kecil : Ekor (Cauda)

Terdapat kumpulan sel disebut pulau-pulau Langerhansyang berisi sel Beta dan mengeluarkan hormon Insulin.

Disamping sel Beta terdapat sel Alfa yang mengeluarkanGlukagon yang bekerja berlawanan dengan insulin yaitumeningkatkan kadar gula darah. Juga ada sel Delta yangmengeluarkan Somatostatin


45/190


46/190


47/190

KERJA FISIOLOGIS INSULIN

& PENGLEPASAN INSULIN

Insulin dibentuk dari pro insulin distimulasi dg peglukosa darah menghasilkan insulin & C-peptide ygakan masuk ke dlm aliran darah & akan mekan kadar

glukosa darah Insulin membantu meningkatkan sintesa protein,

meningkatkan penyimpanan lemak, menstimulasimesuknya glukosa ke dlm sel utk sumber energi dan

membantu penyimpanan glikogen dlm lemak dan hati Insulin : endogen & eksogen


48/190

Insulin

Tenaga

Glukosa darah Pintu masuk sel

Insulin

Insulin Insulin

Glukosa dibakar

pembawa glukosa

NORMAL

Insulin InsulinPintuterbuka


49/190

Insulin

Tenaga

Glukosa darah Pintu masuk sel

Tak ada yang dibakar

Pembawa glukosa

DIABETES

Pintutertutup

Glukosa darah

60 ng/ml


50/190

F A S E 1 F A S E - 2

F A S E - 1 F A S E - 2

Individu normal

Penderita DM tipe-2

Insulinplasma

waktu

Insulin

plasma

(Tumpul) (Lebih tinggi dan lama)

(Delayed Insulin secretion) Waktu

3-5 mnt50-60 menit


51/190

100

80

60

40

20

0

Years from Diagnosis

Beta-CellFunct

ion(%)

Beta-Cell Function in the UKPDS

-12 -10 -8 -6 -4 -2 0 2 4 6

Diagnosis


52/190

KERJA FISIOLOGIK INSULIN

MEMASUKKAN GLUKOSA DARI DALAM DARAH KE: Hati:

Glukosa di robah jadi glikogen (Glikogenesis)

Glikogen hati menjadi cadangan gula dalam tubuh

Otot:

Glukosa di robah jadi Glikogen (Glikogenesis)

Glikogen otot dibakar menjadi sumber kalori.

Adiposa: Glucosa dirobah (?) jadi trigliserida

Mencegah pemecahan lemak (Antilipolisis)

Mengaktifkan Lipoprotein Lipase di sel sel endotel P.darah

Jaringan lain: Meningkatkan sintesa protein dari A.Amino

INSULIN MENURUNKAN KADAR GLUKOSA DARAH

UKPDS :


53/190

SlametS53

100

75

50

25

0

UKPDS :Natural Deterioration of -Cell Function


Lebovitz H. Diabetes Review 1999;7:139-53

Be

taCellF

unction(%)

-12 10 -6 -2 0 2 6 10 14

Th/Expectation

Facts

Strategy to Prevent the Deterioration


54/190

gyof Type 2 Diabetes



T2DM phase III

Beta Cell

Function

(%)IGT Postprandial

Hyperglycemia

T2 DM

phase I T2DM

phase II

-1210 -6 -2 0 2 6 10 14

MonotherapyLife StyleOral Hypo(s)

Combination

Insulin with

or without

Oral Hypo

Glycemic agent

Hyperglycemia


55/190

SlametS55

Hyperglycemia

Glucose autoxidation Sorbitol pathwayrAGE formation

Oxidative Sress

Antoxidants

Lipid peroxidationLeukocyte adhesionFoam cell formation

TNF a

Endothelial dysfunctionNO EndothelinProstacyclinTXA2

HypercoagulabilityFibrinolysisCoagulability

Platelet reactivity

Vascular complications

Retinopathy Nephropathy Neuropathy


56/190

Stehouwer CDA et al. 2004

ffect of Hyperglycemia

Oxidative stress

Sorbitolpathway

DAG-PKCpathway

Hexosaminepathway

AGEpathway

Increase of : Extracellular

matrix

Collagen

Fibronectin

Increase of pro-coagulant proteins

von Willebrandt

factor

tissue factor

Decrease ofproliferation,migration,

and fibrinolyticpotential

Increase ofapoptosis

Vascular complications


57/190

INSULIN DALAM JUMLAH YANG NORMAL TIDAK DAPAT BEKERJA SECARA

OPTIMAL DI JARINGAN SASARAN NYA

SEPERTI DI OTOT, HATI DAN ADIPOSA.

Sel sel pancreas mengkompensasi keadaan ini

dengan meningkatkan produksi insulin dan me

nyebabkan HIPERINSULINEMIA


58/190

Insulin Resistance

I li ti I li i t


59/190

Hyperglycemia (Type 2 DM)

Increase LipolysisDecrease Lipogenesis

Adipose tissue

(Obesity)

Elevated

Plasma

FFA

Elevated

TNF-a

Insulin secretion Insulinresistance

Hyperinsulinemia

Amyloid deposit

Islet -cell degranulation;

Reduced insulin content

Reduced plasmainsulin

Increased hepatic

glucose output

+

-

Gluconeo

genesis

decreased

glucose uptake

Glucosetoxicity

Lipotoxicity


60/190

Glucose Transporters

GLUT1 : Endothelium

GLUT2 : Liver, B-cells of Pancreas

GLUT3 : Neurons GLUT4 : Muscle, Adipose Tissue

GLUT5 : Intestine


61/190

Insulin functions to promote transmembrane


62/190

Copyright 2008 Dr. Salme Taagepera, All rights reserved.

ptransport of glucose into the cell

1. Binding of insulinto the cells insulin

receptor causes the receptorto become

activated (autophosphorylation)

2. The activated receptor, in turn, activates

a signaling pathway

(IRS-1 PI3-kinase PDK Akt)

3. The activated signaling pathway causes

the translocation of the intracellular

GLUT4 transporterto the cell surface

4. NET RESULT: GLUT4 (insulin-responsive) glucose transporters import

glucoseacross the membrane into the

cell

1

23

4


63/190

Insulin ResistanceGl


64/190

PPARg

promoterCoding reg

+RXR

Modified from Howard L. Foyt et al. Thiazolidinediones. Diabetes Mellitus: a Fundamental and Clinical Text, 2ndEd.

PPRE

Insulin Glucose

mRNA

Synthesis GLUT 4

X

X

transcription

Insulin

receptor

Translocation

Muscle

Cells

Physiological Serum Insulin


65/190

4:00

25

50

8:00 12:00 16:00 20:00 24:00 4:00

Breakfast Lunch Dinner

Plasmainsu

lin(U/ml)

Time

8:00

Physiological Serum InsulinSecretion Profile

Type 2 Diabetes is NOT a mild


66/190

Diabetic

retinopathy

Leading cause

of blindness

in working-age

adults1

Diabetic

nephropathy

Leading cause ofend-stage renal disease2

Cardiovascular

disease

Stroke

1.2- to 1.8-fold increasein stroke3

Diabetic

neuropathyLeading cause of non-

traumatic lower

extremity amputations5

75% diabetic patients

die from CV events4

Type 2 Diabetes is NOT a mild

disease

1Fong DS, et al.Diabetes Care.2003; 26 (Suppl. 1): S99S102. 2Molitch ME, et al.Diabetes Care.2003; 26 (Suppl. 1): S948.3Kannel WB, et al.Am Heart J.1990; 120: 6726. 4Gray RP & Yudkin JS. In Textbook of Diabetes 1997.

5Mayfield JA, et al.Diabetes Care.2003; 26 (Suppl. 1): S78S79.

Microvascular Macrovascular


67/190


68/190

Chronic Complications-


69/190

pMicrovascular :

1. Diabetic Retinopathy



70/190

Chronic ComplicationsMicrovascular

2. Nephropathy



71/190

Chronic ComplicationsMicrovascular

3. Diabetic Neuropathy

Cli i l t


72/190

Clinical assessment

symptoms and signsmay be obvious or subtle

- history of rest pain at night

- gangrene

colour- white

- red (hyperaemic skin)

temperature

- cool

Pulses and ABPI


73/190

Effects on Blood Vessels


74/190

Effects on Blood Vessels

Blood Vessel

Lumen

Chronic Complications-Microvascular


75/190

Chronic Complications Microvascular

Sexual problems for men

erectile dysfunctionretrograde ejaculation

Sexual problems for women

decreased vaginal lubricationdecreased sexual response

Urologic problems for men andwomen

urinary tract infectionsneurogenic bladder

R l ti f Bl d S

FeedbackEndocrine System Control


76/190

liver

pancreas

liver

Regulation of Blood Sugar

blood sugar level(90mg/100ml)

insulin

bodycells takeup sugarfrom blood

liver storessugar

reducesappetite

glucagon

pancreas

liverreleasessugar

triggershunger

high

low

FeedbackEndocrine System Control

GEJALA KLASIK DM


77/190

GEJALA KLASIK DM

4 P

1. POLI DIPSIA

2. POLIFAGIA

3. POLI URIA

3. PENURUNAN BERAT BADAN

Signs and Symptoms


78/190

Signs and Symptoms

Klinis Diabetes Melitus :


79/190

Klinis Diabetes Melitus :

Polifagia : sel mengalami starvasi karena cadangan

KH,Lemak, Protein berkurang ( tdk ada pengisian depot ygbiasanya dilakukan oleh Insulin )

Polidipsia : glukosuria (diuresis osmotik) dehidrasiintraselular dan stimulasi pusat haus di hipotalamus)kompensasi: penderita banyak minum

Poliuria : glukosuria (diuresis osmotik) penderitabanyak kencing

Penurunan BB : cairan tubuh berkurang karena diuresisosmotik, protein dan lemak berkurang karena dipecah sbgsumber energi.

Lelah : Metabolisme tdk berjalan sebagaimana mestinya.


80/190

Diabetes


81/190

Diabetes

Fasting Plasma Glucose

7.0mmol/l(126mg/dl)

Or 2 hour plasma glucose 11.1 mmol/l

(200mg/dl)

OGTT


82/190

OGTT

TEST TOLERANSI GLUKOSA


83/190

ORAL (T.T.G.O)

1. Makan minum seperti biasa 3 hari sebelumpemeriksaan2. Kegiatan jasmani dilakukan seperti biasa3. Berpuasa 10-12 jam sebelum pemeriksaan4. Pagi diperiksa KGD puasa

5. Minum larutan 75 gr glukosa dalam 250cc air (5 menit)6. Pasien menunggu selama 2 jam dan tidak merokok7. Diperiksa KGD 2 jam sesudah minum larutan glukosa

TGT KGD puasa normal. KGD 2 jam paska pembebanan 75 gram glukosa antara 140-199 mg%

GDPT KGD Puasa 110-125 mg%,KGD 2 j PG Normal.

GEJALA KLINIS DIABETES MELLITUS


84/190

TIPE-2

GEJALA KHAS GEJALA TIDAK KHAS

Poliuria Kesemutan

Polidipsia Gatal di daerah genital

Polifagia Keputihan

BB turun cepat Infeksi sukar sembuh

Bisul hilang timbul.Penglihatan kaburCepat lelah

Mudah mengantuk

Complications of Diabetes Mellitus


85/190

Complications of Diabetes Mellitus

Chronic Complications of

Diabetes MellitusMicrovascular Retinopathy

(nonproliferative/proliferative)

Nephropathy Neuropathy Sensory and motor

(mono- andpolyneuropathy)

Autonomic

Macrovascular Coronary artery disease Peripheral vascular

disease Cerebrovascular disease

Acute Complications of

Diabetes MellitusHyperglycemia crisis Diabetic ketoacidosis Hyperglycemia

hyperosmolar State

Lactic acidosisHypoglycemia


86/190

KARAKTERISTIK


87/190

DM TIPE 1DAN DM TIPE 2

DM TIPE 1

Mudah terjadi ketoasidosis

Pengobatan harus dgn insulin

Onsetnya akut

Biasanya kurus /Umur muda Terkait dgn HLA-DR3 & DR4

ICA; GADA; & IAA selalu (+)

Riwayat keluarga (+) pd 10%

30-50% kembar identik terkena

DM TIPE 2

Jarang ketoasidosis (HONK bisa)

Tidak mesti diberi insulin

Onsetlambat (pelan-pelan)

Gemuk atau tak gemuk / > 45 thn Tak ada kaitan dengan HLA

Tak ada autoantibodi

Riwayat keluarga (+) pada 30%

100% kembar identik terkena

Kriteria Pemantauan Diabetes


88/190

Mellitus

BAIK LUMAYAN BURUK

KGD puasa 80-109 110-139> 140

KGD 2 jam pp 110-159160-199 > 200

HbA1c* 4 - 5.9% 68% > 8%

Kolesterol total* < 200 200-239 > 240Kolest. LDL (PJK-)* < 130 130-159 > 160

Kolest.LDL (PJK+)* < 100 100-129 > 130

Trigliserida (PJK-)* < 200 200-249 > 250

Trigliserida (PJK+)* < 150 150-199 > 200

* = diperiksa tiap 3 hingga 6 bulan

Glycated Hemoglobin (HbA1c)


89/190

1


90/190


91/190


92/190

Hyperglycemia

Drowsy

Flushed Thirsty


93/190

Diabetic Emergencies According

to Blood Glucose Level


94/190

Signs of Diabetic Coma Kussmaul respirations Dehydration

Fruity breath odor

Rapid, weak pulse Normal or slightly low blood pressure

Varying degrees of unresponsiveness


95/190

Symptoms of Hypoglycemia


96/190

Symptoms of Hypoglycemia

Heatpalpitations

Confusion

Tremor Sweating

Anxiety

Hunger

Visual

disturbances Seizure

Loss of

Consciousness

Hypoglycemia
http://images.google.ca/imgres?imgurl=http://www.cdc.gov/diabetes/pubs/images/sugarp1.gif&imgrefurl=http://www.cdc.gov/diabetes/pubs/tcyd/ktrack.htm&h=187&w=200&sz=4&hl=en&start=8&tbnid=FOyk6r9qODE0XM:&tbnh=97&tbnw=104&prev=/images?q=sweating&svnum=10&hl=en&lr=


97/190

Hypoglycemia

Symptoms of hypoglycemiaNeurogenic (autonomic) Neuroglycopenia

Trembling

PalpitationsSweating

Anxiety

Hunger

NauseaTingling

Difficulty concentrating

ConfusionWeakness

Drowsiness

Vision changes

Difficulty speakingHeadache

Dizziness

tiredness

D i t d ith H l i
http://images.google.ca/imgres?imgurl=http://www.cdc.gov/diabetes/pubs/images/sugarp1.gif&imgrefurl=http://www.cdc.gov/diabetes/pubs/tcyd/ktrack.htm&h=187&w=200&sz=4&hl=en&start=8&tbnid=FOyk6r9qODE0XM:&tbnh=97&tbnw=104&prev=/images?q=sweating&svnum=10&hl=en&lr=


98/190

Drugs associated with Hypoglycemia

ACE inhibitorsAlcohol

Antimalarials

Beta-blockers (non-cardioselective) Disopyramide

Fluoroquinolones (e.g. gatifloxacin)

Quinidine Salicylates (high doses only)

Hypoglycemia Treatment
http://images.google.ca/imgres?imgurl=http://www.piperreport.com/archives/Images/Drugs%20from%20Rx%20Bottle.jpg&imgrefurl=http://www.piperreport.com/archives/categories/15.html&h=573&w=837&sz=297&hl=en&start=4&tbnid=v5gprWHyGL7seM:&tbnh=99&tbnw=144&prev=/images?q=prescription+bottle&svnum=10&hl=en&lr=


99/190

Hypoglycemia Treatment

Glucose 15 grams of simple carbohydrates

8oz. fruit juice

Half can regular soda

3 glucose tabs

1 tablespoon honey

Glucagon injection

Stimulates glycogen breakdown

Baseline Vital Signs


100/190

Baseline Vital Signs

Hypoglycemia Respirations = normal to rapid Pulse = normal to rapid Skin = pale and clammy

Blood pressure = low Hyperglycemia

Respirations = deep and rapid Pulse = normal to fast

Skin = warm and dry Blood pressure = normal


101/190

MANAGEMENT OF DM


102/190

MANAGEMENT OF DM

Regular Blood Glucose Monitoring

iet

Exercise

rug Therapy

102

Management: Diet & Exercise


103/190

Management: Diet & Exercise

Edukasi


104/190

Edukasi

Tujuan:

Pencegahan PrimerPencegahan Sekunder

Pencegahan Tertier


105/190

MICROVASCULARCOMPLICATIONS


106/190


107/190

Diabetic retinopathy


108/190

Diabetic retinopathy

108

Two types of diabetic retinopathy:

Nonproliferative diabetic retinopathy (NPDR)

Early stage diabetic retinopathy

Proliferative diabetic retinopathy (PDR)

Later stage diabetic retinopathy


109/190


110/190


111/190

DIABETICNEPHROPATHY


112/190


113/190


114/190

DIABETICNEUROPATHY

Mechanism of nerve damage indiabetes


115/190

diabetes

METABOLIC VASCULAR

glucose

sorbitol

H2O

nerve

oedema

myoinositol

NO

production

AGE

formation

vasoconstriction

Arterialnarrowing

Vessel

occlusion

Slow nerve

conduction

Impairing

axonal transport

Altered membrane

potensial


116/190

Burning, feeling like the feet are on fire Freezing, like the feet are on ice,

although they feel warm to touch

Stabbing, like sharp knives Lancinating, like electric shocks


117/190

Autonomic Neuropathy


118/190


119/190

Case 4


120/190



121/190

Microvascular

Amputation of Toes
http://www.iwgdf.org/Images/footnotes/case%201%20ulcer%20post%20amputation.JPG


122/190

Charcot foot

grossly disorderedarchitecture andbiomechanics

midfoot ulceration

instability of midfoot

note previous minoramputations

still well-vascularised


123/190


124/190


125/190

Bone resorption and destruction


126/190

Bone regeneration on antibiotic therapy


127/190


128/190



129/190

Sexual problems for men

erectile dysfunctionretrograde ejaculation

Sexual problems for women

decreased vaginal lubricationdecreased sexual response

Urologic problems for men and

women

urinary tract infectionsneurogenic bladder


130/190

MACROVASCULARCOMPLICATIONS

5. KOMPLIKASI DIABETES


131/190

Diabetic

Retinopathy

Leading causeof blindnessin working ageadults1

Diabetic

Nephropathy

Leading cause of

end-stage renal disease2

Cardiovascular

Disease

Stroke

2 to 4 fold increase incardiovascularmortality and stroke3

Diabetic

Neuropathy

Leading cause ofnon-traumatic lowerextremity amputations5

8/10 diabetic patientsdie from CV events4

1 Fong DS, et al.Diabetes Care2003; 26 (Suppl. 1):S99S102. 2Molitch ME, et al.Diabetes Care2003; 26 (Suppl. 1):S94S98.3Kannel WB, et al. Am Heart J1990; 120:672676. 4Gray RP & Yudkin JS. In Textbo ok of Diabetes 1997.

5Mayfield JA, et al.Diabetes Care2003; 26 (Suppl. 1):S78S79.

PEMBULUH DARAH KECIL PEMBULUH DARAH BESAR


132/190

KONTROL Kadar Gula DarahADEKWAT

TERBUKTI MENURUNKAN RISIKOKOMPLIKASI KRONIS

Hubungan kegagalan terapi dg Stadium pada DMTipe 2 dan Fungsi Sel Beta Pankreas


133/190

100

75

50

25

0

-12 -10 -6 -2 0 2 6 10 14

Fungsi selBeta (%)

Tahun Sejak Diagnosis

TGTHiperglikemiPostprandial Fase I

DM tipe 2Fase II

DM tipe 2

Fase IIIDM tipe 2

p g

Strategy to Prevent the Deteriorationof Type 2 Diabetes


134/190



T2DM phase III

Beta Cell

Function(%)

IGT PostprandialHyperglycemia

T2 DM

phase I T2DM

phase II

-1210 -6 -2 0 2 6 10 14

MonotherapyLife StyleOral Hypo(s)

Combination

Insulin with

or without

Oral Hypo

Glycemic agent

Matching Pharmacology toPathophysiology


135/190

p y gy

Hyperglycemia

Biguanides

(TZD)

TZD

(Biguanides)

Alpha-glucosidase

inhibitorsSulfonylureas

Meglitinides

Nateglinide

Glucose influx

Peripheralglucose uptake

Insulinsecretion

Hepaticglucoseoutput

Site & Mode of Action of OADs


136/190

136 www.drsarma.inAdapted from DeFronzo R. Ann Intern Med 1999;131:281

Site of action MOA Agents

Insulinsecretion

Sulfonylureas

Repaglinide

Nateglinide

HGOproduction

BiguanidesGlitazones

Slow CHO

Digestion

a- glucosidaseinhibitors

Peripheralinsulin sensitivity

GlitazonesBiguanides

SUS: Mechanism of action


137/190

Others:Dec glucagonSecretionBinding toExtrapancreaticSU receptors

in K channels

Actions of Metformin


138/190

Dr.Sarma@works

REPAGLINIDE:Mechanism of action


139/190

Mechanism of action

Meglitinides: have 2 common binding sites

w/ SU and 1 unique binding site


140/190


141/190

GLP-1 MIMETIC:EXENATIDE


142/190

EXENATIDE

SC injections: absorbed equally from arm,abdomen, thigh

Peak: 2 hrs

Duration: up to 10 hrs

DPP-IV INHIBITORS


143/190

Sitagliptin

When to start insulin?BMI 23 M tf i AGI TZD DPP IV


144/190

BMI : > 23 Metformin, AGI, TZD, DPP-IV

Inh. BMI: 1823 Metformin, SU/glinid, AGI, DPP-IV

Inh.

BMI: < 18 InsulinHbA1c :

< 7 life style modification

78 single/combination oral drugs

89 combination oral drugs

> 9 oral drug + insulin combination

intensive insulin

Sejarah Insulin


145/190

1921 Insulin ditemukanoleh Banting dan Best

1922 Leonard Thompsonadalah pasien pertama yangmendapat suntikan insulin

1923 Novo Nordiskmulai

produksi Insulin Hewan(Sapi dan Babi)

1973 Insulin HewanMonokomponen

1987 Insulin Human 1990 Insulin Analog

INDIKASI PENGGUNAAN INSULIN

1 DM tipe 1


146/190

1. DM tipe 1

2. Penurunan berat badan yg cepat

3. Hiperglikemia yg berat disertai dg ketosis

4. Ketoasidosis diabetik

5. Hiperglikemia hiperosmolar non ketotik

6. Hiperglikemia dg asidosis laktat7. Gagal dg kombinasi OHO dosis hampir max

8. Stress berat

9. Kehamilan dg DM atau DM Gestasional

10. Gangguan fs. ginjal atau hati yg berat11. Kontraindikasi dan atau alergi thp OHO

KEGUNAAN METABOLIK TERAPI INSULIN


147/190

Menurunkan kadar GD puasa & pp Supresi produksi glukosa oleh hati Stimulasi utilisasi glukosa perifer oksidasi gluk / penyimpanan di otot Perbaiki komposisi lipoprotein abnormal Mengurangiglucose toxicity Perbaiki kemampuan sekresi endogen

Mengurangiglycosilated end products

KAPAN INSULIN DIPERLUKAN?


148/190

Data UKPDS :50% DMT2 perlu insulin setelah 6

tahun

Fungsi B-cell yg rendah pd saatdiagnosis risiko kegagalan OHOlebih tinggi

Marre M. Int J Obesity (2002) ; 26 (Suppl 3) : S25-S30

Modern "Aggressive" Rx of Type 2DM from Time of Diagnosis


149/190

g

HbA1c > 10 % or

FPG >260 mg/dl

or Symptomatic

or

Ketotic

IMMEDIATE INSULIN

Modern "Aggressive" Rx 4


150/190

HbA1c not < 7% by6 months Start

Insulin

Insulin Preparations


151/190

www.drsarma.in 151

Rapidity of Action Insulin preparation

Ultra- rapid-action

Onset 10 -20 Peak 30 min

Lispro (Humalog), Glulisin (Apidra)

Aspart (Novolog)

Short Acting

Onset 30 to 60, Peak 2 hr

Regular (Human) Insulin

Humulin R, Novolin RIntermediate Acting (Human)

or Analog 1 -4 h, Peak 4 -10 h

NPH (Human) Humulin N, Novolin N

Insulin Detemir (analog) - Levemir

Long Acting 1-3 No Peak 24 h Insulin Glargine (Lantus)

Mixtures (Human)1 h, P 3-12 h 70/30 or 50/50 Humulin, 70/30 Novolin

Mixtures (Analog)

Onset 30-1h, Peak 3-12 h

75/25 or 50/50 Humalog (NPL + Lispro)

70/30 Novolog neutral (Protamin + Aspart

HUMAN INSULIN


152/190

A chainGly II

eVal Glu Gln Cys Cys Thr Ser Ile Cys Ser Leu Tyr Glu Leu Glu Asn Tyr Cys Asn

1 5 10 15 21

S S

1 5 10 15 20

25

30

B chainS

S S

S

Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg GlyPhe

PheTyrThr

LysPro

The

Phe

HUMAN INSULIN

Human insulinA chain 21 amino acidsB chain 30 amino acids

J NIS INSULIN


153/190

Natural (animal) insulin: ekstraksi dari pankreas hewan Semisynthetic human insulin: insulin dari hewan yg dimodifikasi secara

enzimatik

Biosynthetic human insulin: dibuat dengan DNA rekombinanmenggunakan ragi atau bakteri

Insulin analog: biosynthetic human insulinyg direkayasa dgnmempertukarkan posisi asam amino atau menambahkan satu atau lebihasam amino/asam lemak pada rantai molekul insulin

Tipe insulin berdasarkan puncak dan


154/190

p pjangka waktu kerjanya :

1. Insulin kerja sangat cepat : NovoRapid, Humalog,Apidra

2. Insulin kerja pendek : , Humulin R

3. Insulin kerja sedang : , Humulin N4. Insulin campur : , Humulin 30/70, NovoMix 30,

Humalog 25

5. Insulin kerja panjang : Levemir, Lantus

Kendala Terapi Insulin


155/190

Adanya anggapan : Sekali dimulai, tidak pernah bisa berhenti Akan membatasi aktivitas sehari-hari Memulai terapi Insulin berarti:

Saya telah gagalDM-nya sudah menjadi serius

Suntikan insulin akan sangat sakit/nyeri Suntikan insulin menyebabkan kebutaan Franks story: Jika anda tidak bekerja keras, anda

akan saya suntik insulin lho

Prinsip Terapi


156/190

Insulin Basalmenurunkan gula darahpuasa

Insulin Bolus

menurunkan gula darahpost prandial(setelah makan)

Insulin Premixedmenurunkan GD

puasa dan GD 2 jam PP

Macam-macam Rejimen Insulin


157/190

Basal Bolus4 suntikan per hari (3 bolus dan 1 basal)

Satu kali suntikan insulin basalpada malam

hari ditambah dengan obat oral

Premixed Insulin, sekali sampai 3 kali sehari,sebelum makan.

Premixeddikombinasi denganshort acting

4 Suntikan per Hari3 Short+ 1 Intermediate/Long Acting(B l B l )


158/190

(Basal Bolus)

6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5

Breakfast Lunch Evening Meal Sleep

time

Dua kali Suntikan Prem ixed Insul inPer Hari


159/190

6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5

Breakfast Lunch Evening Meal Sleep

time

Tempat Penyuntikan Insulin Subkutan :Searah Jarum Jam


160/190

45 -60 31 -45

61 - 75 16 -30

75 -90 1 -15

Continuous IV insulin infusion

Used to maintain glycemic control in


161/190

Used to maintain glycemic control inhospitalized patients with high blood

glucose levels; in DKA and HHNS

Regular insulin may be used IV

May also be given preoperatively orpostoperatively

More frequent BS monitoring ( q1-2

hours per agency protocol)

Efek Samping Insulin


162/190

Hipoglikemia (kadar glukosa darah terlalurendah)

Peningkatan berat badan

Reaksi Alergi (kemerahan, gatal-gatal di tempat

penyuntikkan) Lipodistrofi

DIABETESDAN PERAN INSULIN DALAM PENANGANANNYA


163/190

DAN PERAN INSULINDALAM PENANGANANNYA

Dr. SUHAEMI, SpPD, FINASIM

Leonard Thompson


164/190

1922 1923

Meninggal tahun 1935

Perkembangan Terakhir Injeksi Insulin


165/190

Non-Injectable Insulin


166/190

Trans-dermal insulin delivery

Oral insulin delivery

Buccal insulin deliveryPulmonary insulin delivery

Insulin Delivery Devices 3
http://www.generex.com/images/rapidmistrollover


167/190

Inhaled Insulin


168/190

Exubera

Inhaled Insulin


169/190

1-1-08

voluntary discontinuation

4-6-08

Cancer Warning

Exubera (Inhaled Insulin)


170/190

171www.drsarma.in

Insulin Blistersfor Aerosol

Other Injectable Drugs 1


171/190

Exenatide (Byetta)

insulin secretagogue

peptide

gila monster saliva use with other drugs

no hypoglycemia

bid

Exenatide (Byetta)


172/190

www.drsarma.in 173

Other Injectable Drugs 1


173/190

j g

Pramlintide (Symlin) analogue of hormone

amylin

polypetide

slows gastricemptying

induces satiety

opposes glucagonreduces posprandialBG

give with meals used with insulin

Exenatide


174/190

www.drsarma.in 175

We have two hormones in intestines - IncretinsGLP-1 (Glucagon Like Peptide-1) and

GIP (Glucose dependent Insulinotropic Polypetide)

Normally Incretins are degraded by DPP IV enzyme Exenatide is a synthetic analog of GLP-1Mimetic

It is very similar to the GLP-1 in venom of Gila mon.

This is resistant to degradation by DPP IV enzyme Exenatide inj. enhances postprandial insulin secretion

Liraglutide


175/190

www.drsarma.in 176

Modified GLP-1 Binds to albumin

Injection form only

Can reduce fasting and PP hyperglycemia

It is an additional Rx. option

Can be combined with OADs

Does not cause hypoglycemia.

SitagLiptin


176/190

www.drsarma.in 177

Normally Incretins are degraded by DPP IV enzyme Liptins are compounds which inhibit the DDP IV

Liptins increase the action of natural GLP-1

These are oral drugshence advantageous These postprandial insulin secretion via GLP-1

Sitag-liptin, Vildag-liptin, Sexag-liptinare useful Rx

They are 2ndline agents. Combined with OADs

Do not cause hypoglycemia.

Future Therapies

1. RIMONABANT CB1- R blocker Obesity thus


177/190

www.drsarma.in 178

y

DM

2. GLITAZARsDual PPAR activatorGlycemia,Lipids

Muraglitazar, Tesaglitazar, Ragaglitazar

3. VOGLIBOSENew a-GI Inhibitor - PPBG

4. ACIPIMOX FFA and IR - FBG

5. PIMAGIDINE AGPs & prevents DM complications

6. ZENERESTAT Sorbitol & Fructose DM PNP

7. ZOPOLRESTAT Aldose Red. DM PNP8. Acetyl L-Carnitine NCV DM PNP/ ANP

9. BIMOCLOMOL Heat Shock Proteins DR & DKD

10. EXO- 226 Glycation of Proteins DKD

Future Diagnostic Tests


178/190

www.drsarma.in 179

Glucose sensorsto be applied on to skin Peel of patch testsRead the Sugar in sweat

Micro needle inserted continuous monitors

Antibodies to insulin for insulin resistance HbA1c monitorslike glucose monitors

SMBG


179/190

Value in Type 2 DMnot established

Useful for titrating

insulin

Glycated Hemoglobin (HbA1c)2


180/190

Insulin


181/190

AcuteComplication:

Hypoglycemia

Tx: (15/15 or 20/20

Rule)

Give 15/20 g simple

carb and recheck

BG in 15/20 minutes

InsulinAcute ComplicationHypoglycemia


182/190

Hyperglycemia


183/190

How to preventionComplications of Diabetes ?


184/190

www.drsarma.in 185

1. Weight reduction, Exercise2. Strict control hyperglycemia

3. Achieving lipid profile targets

4. Smoking cessation

5. Rx. of Hypertension with ACEi/ ARB

6. Low dose aspirin therapy

7. Statin therapy for all T2DM

8. ACEi or ARB for all with MAU9. Early detection and evaluation

Treatment of Dyslipidemia


185/190

www.drsarma.in 186

Every T2DM must get 10 mg of Atorvastatin LDL is raisedStatin or Statin+ Ezetemibe

TG is raisedFenofibrate

HDL is lowNiacin Combined dyslipidemiaCombinations

Lp(a) is raisedNiacin

hs-CRP is raisedAspirin & Statin (already)

Take Home

A B C D E


186/190

www.drsarma.in 187

A A1ctarget of < 7%; Better 6%Aspirin for all DM

ACEi or ARB for all DM

B Blood Pressure target of 130/80

Blood Glucose monitoring

C Cholesterol LDL


187/190

Gula Darah Puasa

Gula Darah 2 JSM

HbA1C (%)

Kolesterol Total

Kolesterol LDL

Kolesterol HDL

Trigliserida

BMI

Tekanan Darah

80 - 100

80 - 144

< 6,5

< 200

< 100

> 45

< 150

18,5 - 22,9

< 130 / 80

BAIK

100 - 125

145 - 179

6.5 - 8

200 - 239

100 - 129

150 - 199

23 - 25

130-140/ 80-90

SEDANG

> 126

> 180

> 8

> 240

> 130

> 200

> 25

> 140 / 90

BURUK


188/190


189/190


190/190

Documents

Diabetes Mellitus.kuliah2013