Diabetes Mellitus 2017

 

DIABETES MELLITUS Dr. SUHAEMI, SpPD, FINASIM

 

Diabetes Mellitus Suatu Sindroma kelainan metabolik, ditandai adanya hiperglikemia, akibat defek sekresi insulin, defek kerja insulin, atau kombinasi keduany keduanya.

 

Class Classification ification of Diab Diabetes etes 

Type 1 diabetes 



Type 2 diabetes 



β-cell destruction

Progres Pr ogressive sive insulin secret secretory ory defect defect

Other specific types of diabetes 

Genetic defects in β-cell function, insulin action



Diseases of the exocrine exocrine pancreas  Drug- or chemical chemical-in -induc duced ed 

Gestational diabetes mellitus

ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S12.

 

Diabetes Mellitus : a group of diseases characterized by high levels of blood glucose resulting from defects 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 diabetes 2) Type 2 diabetes 3) Gestational diabetes

 Complications : - Stroke - He Hear artt att attac ack k - Kid Kidney ney dis diseas ease e - Ey Eye e Dis Disea ease se - Ne Nerv rve e Dama Damage ge

 

Diabetes Mellitus 

Type 1 Diabetes - cells that that produce produce insul insulin in are destroyed - resu results lts in insuli insulinn dependence dependence - common commonly ly detected detected befo before re 30



Type 2 Diabetes - blood glucos glucose e levels levels rise rise due to 1) Lack of insulin production 2) Insufficient insulin action (resistant cells) - commo commonly nly detecte detected d after after 40 - ef effe fect ctss > 90% 90% - eve eventual ntually ly leads to β-cell failure (resulting in insulin dependence)

Gestational Diabetes 3-5% of pregnant women in the US develop gestational diabetes

 

Diabetes Mellitus Type 1 





Results from inability of islet cells to produce insulin Also known as insulindependent or juvenile-onset diabetes Cause is unknown, unknown, but likely to have genetic, autoimmune component

 

Diabetes Mellitus Type 2 

Results from decreased insulin sensitivity and decreased pancreatic betacell function

 

Gestational Diabetes 





Diabetes that first presents during pregnancy Occurs in 2-10% of pregnancies 30-60% chance of developing T2DM

 

Pathophysiology of T1DM

antibodies attack islets!

 

986 NEJM “Stages” in Development of Type Diabetes (?Precipitating Event)

Genetic Predisposition

  s   s   a   m    l    l   e   c   a    t   e    B

Overt immunologic abnormalities

Normal insulin release

Progressive loss insulin release Glucose normal

Overt diabetes

C-peptide present

Age (years)

No C-peptide

 

Stages Type IA Diabetes 

I

Genetic Susceptibility



II Triggering



III Active Autoimmunity



IV Progressive Metabolic Abnormalities



V Overt Diabetes



VI Insulin Dependence

 

Environment Congenital Rubella  Controversy re Enteroviruses other virus  Controversy re bovine milk  Hygiene Hypothesis 



2 JAMA papers re early cereal

 

Etiology of Autoimmune Diabetes 

Genetic susceptibility susceptibility   







Lifetime risk in general population: 0.4% Up to 50% concordance concord ance in monozygotic twins Sibling risk: 5%, Father to child risk: 6-12%, Mother to child c hild risk: 4% if 25 years (Risk doubles if parent/sibling was younger young er than 11 at diagnosis.) Associated with HLA DR3/DR4 genes

Environmental trigger 

Incidence more common in fall and winter - viral infection trigger?



Possibly multiple potential triggers in early infancy: viruses, cows milk, toxins

Auto-antibodies: 1 or more present in 85-90% at diagnosis:  GAD 65, islet cell, c ell, insulin and tyrosine phosphatases (IA-2 (IA-2 & IA-2B) antibodies 

GADwhich 65 h(glutamic acid decarboxylase) most common: cell whic shares sequence homology homology with some virusesprotein found in the beta

 

Natural History of Type 2 Diabetes

Plasma glucose

TLC OAD ACEI AIIA

Post-prandial glucose Fasting glucose

  -cell function

OADs Insulin Rx

Insulin resistance Insulin secretion

0

10

 Years  Y ears of Diabetes

20

30

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

RISKESDAS 2008

Indonesian Basic Health Research (RISKESDAS) Total DM = 5,7% Diagnosed DM = 1,5% Undiagnosed DM = 4,2% IGT = 10,2 %

Diagnosed patients

Undiagnosed patients

DM patients estimated (WHO)

8 million million

2000

>21

2030  

Epidemiology of Diabetes

 

Diabetes in the World

31.7 India

Year 2000

20.8 China

17.7 USA

8.4 Indonesia

6.8 millions

Japan

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

¡Viva la Vida con Salud!

 

Diabetes in the World

79.4 India

Year 2030

42.3 China

30.3 USA

21.3 Indonesia

8.9 millions

Japan

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

¡Viva la Vida con Salud!

 

Why is Diabetes on the Increase?  



Ethnicity and family history are implicated Closely associated with overweight or obese people Increased switch to Western diet and lifestyle Obesity

Genetic component

TYPE

2

Western lifestyle

DIABETES

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

Fast Food and Obesity 

200%  fast-food visits 1977-1995



30% of US children (4-19 yrs) consume fast food daily

 

Fast Food and Obesity 

Fast-foods  fat and energy 



Big Mac + medium fries = 83% daily fat intake



Adversely affects dietary quality Less fiber, fruits, vegetables and milk



Mega-meals

 

Mega Mega –   – Meals Meals

 

Super Size 





Each 12 oz soda has 10 tsp sugar (150 cal) One can of soda/da soda/day y child’s risk obesity 60% Most popular Canadian drink 



> 110 L/ person/yr

1942-1998: 

US production increased 9X

 

Maharaja Mac ?

 Jumbo Vadapav? Vadapav?

Double Cheese Pizza?

DO NOT UPSIZE !!!  We  W e Need To To Minimize Not Maximize

 

Oxidative Stress Damages Here Endothelial lining

Smooth muscle Collagen

 

33

Diabetes

Metformin Approved Use Single Therapy

  om bined w it ith h Insuli Insulin n Children Childre n > 1 years Metformi Metfo rmin n dos dose e 45 tahun Gemuk : BB > 120% BBI (IMT > 27 kg/m2) Hypertensi Riway Riwa yat Ke Keluarga luarga DM Riwayat melahirkan bayi > 4 kg. Riwayat DM pada waktu hamil (DM Gestasi) Dislipidemia : HDL < 35 mg/dl, Trigliserida > 250 mg/dl Pernah mengalami gangguan toleransi glukosa

 

Etiologi 



Herediter, diperlukan Herediter, diper lukan faktor lain yang disebut faktor risiko atau faktor pencetus Virus 







Pada DM tipe 1 dijumpai HLA  gen yang rentan terhadap infeksi virus tertentu. Virus yang selalu menimbulkan insulitis insu litis adalah : Coxackie, Coxackie, Mumps, Rubella, Cytomegalovirus, Herpes, dll.

Obesitas  Kadar Insulin cukup tetapi tidak efektif (Resistensi (Resistensi Insulin ) Memakai obat-obatan yang menyebabkan Kadar Gula Darah meningkat

 

Causes of Mortality in Diabetic Patients Myocardial infarction

34.7

Stroke

22

Tumors

10

Infections Diabetic coma

3.1

Renal insufficiency

2.9

Gangrene

2.7

6.7

 Accident / suicide Tuberculosis

2.1 0.9

Others

11.4

Not specified

3.4 0

% deaths in diabetics 10

20

30

40

Panzram G. Diabetologia 1987; 30: 120 -  -31  3   1   

Pankreas      



Terletak dibelakang lambung Berat : 200 –  200 – 250 250 gram Bentuk : Kerucut terbaring Bagian yang lebar lebar : Kepala (Caput) Bagian yang kecil : Ekor (Cauda) Terdapat kumpulan sel disebut pulau-pulau pulau-pul au Langerhans yang yang berisi sel Beta dan mengeluarkan hormon Insulin. Disamping sel Beta terdapat sel Alfa yang mengeluarkan Glukagon yang bekerja berlaw ber lawanan anan dengan insulin yaitu meningkatkan kadar gula darah. Juga ada sel Delta yang yang mengeluarkan Somatostatin

 

INSULIN Definisi : Insulin adalah hormon yang dikeluarkan oleh sel beta  yang berperanan pankreas dalam mengatur kadar glukosa darah Insulin diibaratkan sbg anak kunci yang membuka pintu masuknya glukosa ke dalam sel

 

KERJA FISIOLOGIS INSULIN & PENGLEPASAN INSULIN 





Insulin Insul in d dib iben entu tukk da dari ri pr proo in insul sulin in  di dist stim imul ulas asii dg pe gluk gl ukos osaa da dara rah h    meng menghasilka hasilkann insuli insulinn & C-pe C-peptide ptide yg akan masuk ke dlm aliran darah & akan me kan kadar gluk gl ukos osaa da dara rah h Insul In sulin in me memb mban antu tu me meni ning ngka katk tkan an si sint ntes esaa prot protei ein, n, mening men ingkat katkan kan pen penyimp yimpana anann lem lemak, ak, men mensti stimul mulasi asi mesuknya glukosa ke dlm sel utk sumber energi dan memban bantu penyimp impanan glikogen dlm lemak dan hati Insulin : endogen & eksogen

 

Insulin NORMAL Pintu terbuka

Insulin

Insulin

Insulin Insulin

Insulin

Tenaga Glukosa dibakar

Glukosa darah

pembawa glukosa

Pintu masuk sel

 

Insulin DIABETES

Glukosa darah

Pintu tertutup

Tenaga Tak ada yang dibakar

Pintu masuk sel

Glukosa darah

Pembawa glukosa

 

60 ng/ml Individu normal Insulin  plasma

FAS E 1 3-5 mnt

Insulin

FASE-2 50-60 menit

waktu

Penderita DM tipe-2 (Tumpul)

(Lebih tinggi dan lama)

 plasma FAS E-1

FAS E- 2

(Delayed Insulin secretion)

Waktu

 

KERJA FISIOLOGIK INSULIN 

MEMASUKKAN GLUKOSA DARI DALAM DARAH KE: 

Hati:  











Glukosa di robah jadi Glikogen (Glikog (Glikogenesis) enesis) Glikogen otot dibakar menjadi sumber kalori.

Adiposa: 



Glikogen hati menjadi cadangan gula dalam tubuh

Otot: 



Glukosa di robah jadi glikogen (Glikog (Glikogenesis) enesis)

Glucosa dirobah (?) jadi trigliserida Mencegah pemecahan lemak (Antilipolisis)

Mengaktifkan Lipoprotein Lipase di sel sel endotel P.darah P.darah Jaringan lain: Meningkatkan sintesa protein dari A.Amino

INSULIN MENURUNKAN KADAR GLUKOSA DARAH

 

Strategy to Prevent the Deterioration of Type 2 Diabetes

Life Style

Monotherapy

Oral Hypo(s) Combination

Insulin with or without Oral Hypo Glycemic agent

Beta Cell Function (%) IGT

-12  – 10 10

T2DM phase III

Postprandial T2 DM Hyperglycemiaphase I

-6

-2

0

T2DM phase II

2

6

10

14

 Years  Y ears from Diagnosis Diagnosis Lebovitz H. Diabetes Review 1999;7:139-53  

Hyperglycemia

AGE formation

Glucose autoxidati autoxidation on

Sorbitol pathwayr

 Antoxidants

  Oxidative Sress Lipid pero peroxidation xidation  Leukocyte adhesion  Foam cell formation  TNF a

Endothelial dysfunction  NO  Endothelin  Prostacyclin  TXA2

Hypercoagulability Fibrinolysis  Coagulability  Platelet reactivity

Vascular complications

Retinopathy

Nephropathy

Neuropathy

SlametS

59  

Effect of Hyperglycemia Sorbitol pathway

DAG-PKC pathway

Hexosamine pathway

AGE pathway

Oxidative stress •

Increase of proExtracellular matrixcoagulant proteins

• •

Collagen Fibronectin

Increase of :

• •

von Willebrandt factor tissue factor

Decrease of Decrease proliferation, migration, and fibrinolytic potential

Increase of apoptosis

Vascular complicatio complications ns

Stehouwer CDA et al. 2004

 

INSULIN DALAM JUMLAH YANG NOR MAL TIDAK DAP DAPA AT BEKER BEKERJA JA SECARA OPTIMAL DI JARINGAN SASARAN NY NYA A SEPERTI DI OTOT, HATI DAN ADIPOSA. Sel sel β pancreas mengkompensasi keadaan ini dengan meningkatkan produksi insulin dan me

nyebabkan HIPERINSULINEMIA  

Insulin Resistance

 

The Ominous Octet of DM2 Islet -cell Decreased Incretin Effect Impaired

Increased Lipolysis

Insulin Secretion Islet a-cell

Increased Glucagon Secretion

Increased Glucose Reabsorption

Increased HGP Neurotransmitter  Dysfunction

Decreased Glucose Uptake

DeFronzo RA. Banting Lecture 2008. “From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus.”  

Glucose Transporters GLUT –  GLUT  – 1 1

: Endothelium



GLUT – 2 GLUT –  2 GLUT –  GLUT  – 3 3

: Liv Liver er,, B-cell B-cellss of Pancreas : Neurons



GLUT –  GLUT  – 4 4

: Muscle Muscle,, Adipose Tissue



GLUT –  GLUT  – 5 5

: Intestine





 

Insulin Action Insulin

Glucose

Insulin receptor

PPAR  

RXR

Synthesis GLUT 4 mRNA

PPRE

transcription promoter

Coding reg

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

Insulin Resistance

Glucose

Insulin

Insulin receptor

X

Translocation

X Synthesis GLUT 4 PPAR   +RXR

mRNA

PPRE

transcription promoter

Muscle Cells

Coding reg

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

Physiological Serum Insulin Secretion Profile Breakfast

Lunch

Dinner

   )    l   m    /    U   µ    ( 50   n    i    l   u   s   n    i   a   m   s   a    l 25    P

4:00

8:00

12:00

16:00

20:00

24:00

4:00

8:00

Time  

Type 2 Diabetes is NOT a mild mild disease Microvascular

Macrovascular Stroke

Diabetic retinopathy

1.2- to 1.8-fold 1.8-fold increase increase 3 in stroke

Leading cause of blindness in working-age adults1

Cardiovascular disease 75% diabetic patients die from CV events4

Diabetic nephropathy Leading cause of end-stage renal disease2

Diabetic neuropathy Leading cause of nontraumatic lower extremity amputations5

1

Fong DS, et al. Diabe Diabetes tes Care. Care. 2003; 26 (Suppl. 1): S99 – S102. S102. 2Molitch ME, et al. Diabet Diabetes es Care. Care. 2003; 26 (Suppl. 1): S94 – 8. 8. 3 4 Kannel WB, et al . Am Heart J. 1990; 120: 672 – 6. 6. Gray RP & Yudkin JS. In Te Textbook xtbook of Diabetes 1997. 5Mayfield JA, et al. Diabet Diabetes es Care. Care. 2003; 26 (Suppl. 1): S78 – S79. S79.

 

Chr Chroni onicc Complicat Complication ions-Mi s-Micr crov ovascu ascular lar : 

1. Diabetic Retinopathy

 

Chronic Complications-Microv Chronic Complications-Microvascular ascular 2. Nephropathy

 

Chronic Complications-Microv Chronic Complications-Microvascular ascular 

Gastroparesis

Nerve damage to the digestive system most commonly causes constipation. Damage can also cause the stomach to empty too slowly

 

Chronic Complications-Microv Chronic Complications-Microvascular ascular 3. Diabetic Neuropathy

 

Clinical assessment •

•

•

•

symptoms and signs may be obvious or subtle - histor history y of rest rest pain pain at night night - ga gang ngre rene ne colour  - w hit e - red (h (hype yperae raemic mic skin) skin) temperature - c ool

Pulses and ABPI

 

Effects on Blood Vessels

Blood Vessel Lumen

 

Complicat ions-Microvascular Chronic Complications-Microv ascular 

Sexual problems for men

erectile dysfunction dysfunction retrograde retrograd e ejaculation



Sexual problems for women

decreased vaginal lubrication decreased sexual response



Urologic problems for men and women

urinary tract infections

neurogenic bladder  

Endocrine System Control

Feedback

Regulation of Blood Sugar insulin

liver stores sugar

body cells take up sugar

pancreas

from blood high

liver

blood sugar level (90mg/100ml)

low

triggers hunger

liver releases sugar

pancreas

reduces appetite

liver

glucagon

 

GEJALA KLASIK DM 

4P



1. POLI DIPSIA 2. POLIFA POLIFAGIA GIA



3. POLI URIA



3. PENURUNAN BERAT BADAN



 

Signs and Symptoms

 

Kl Klin inis is Di Diab abet etes es Me Meli litu tuss : 









Pol olif ifag agia ia : sel sel me meng ngal alam amii st starv arvas asii ka karen rena a ca cada dang ngan an KH KH,L ,Lem emak ak,, Prot Pr otei ein n berk berkur uran ang g ( tdk tdk ad ada a pe peng ngis isia ian n de depo pott yg yg bi bias asan anya ya di dila laku kuka kan n oleh ol eh In Insu suli lin n) Pol olid idip ipsi sia a : gl gluk ukos osur uria ia (d (diu iures resis is os osmo moti tik) k) → deh dehidra idrasi si int intrase raselul lular ar dan da n st stim imul ulas asii pu pusat sat ha haus us di hi hipot potal alam amus us)) ko komp mpen ensa sasi si:: pe pende nderi rita ta ban ba nya yak k mi minu num m Pol oliu iuri ria a : gl gluk ukos osur uria ia (d (diu iures resis is os osmo moti tik) k) → pe pend nder erit ita a ba ban nya yak k ke kenc ncin ing g Pen enur urun unan an BB : cai caira ran n tu tub buh be berk rkur uran ang g ka karen rena a di diure uresi siss os osmo moti tik, k, pro pr ote teiin dan dan le lem mak be berk rkur uran ang g ka kare rena na di dipe peca cah h sbg su sum mbe berr en ener erg gi. Lel elah ah : Met eta abo boli lism sme e td tdk k be berj rjal alan an se seba baga gaiiman ana a mes esti tin nya ya..

 

Kriteria Diagnosa DM 





Gejala Klasik DM + Kadar Gula Darah Sew Sewaktu aktu > 200 mg/dl Gejala Klasik DM + Kadar Gula Darah Puasa > 126 mg/dl Kadar Gula Darah 2 jam TTGO > 200 mg/dl



Puasa diartikan kalori tambahan sedikitnya 8 jamtidak TTGOmendapat dengan standar WHO, menggunakan beban glukosa yang setara dengan 75 gram glukosa anhidrous yang yang dilarutkan dilarut kan dalam air

 

Diabetes

  

Fasting Plasma Glucose ≥ 7.0mmol/l(126mg/dl) Or 2 hour plasma glucose ≥ 11.1 mmol/l (200mg/dl)

 

GEJALA KLINIS DIABETES MELLITUS TIPE-2

GEJALA KH KHAS

GEJALA TIDAK KHAS

Poliuria

Kesemutan

Polidipsia

Gatal di daerah genital

Polifagia

Keputihan

BB turun cepat

Infeksi sukar sembuh Bisul hilang timbul. Penglihatan kabur Cepat lelah Mudah mengantuk

 

KARAKTERISTIK DM TIPE 1DAN DM TIPE 2 

DM TIPE 1        

Mudah terjadi ketoasidosis Pengobatan harus dgn insulin Onsetnya akut Biasanya Biasany a kurus /Umur muda Terkait dgn HLA-DR3 & DR4 D R4 ICA; GADA; & IAA selalu (+) Riwayat keluarga (+) pd 10% 30-50% kembar identik terkena ter kena



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 kembar identi identikk terkena terkena

 

Kriteria Pemantauan Diabetes Diabetes Mellitus BAIK

LUMAYAN

BURUK

KGD puasa

80-109

110-139

> 140

KGD 2 jam pp HbA1c* Kolesterol total* Kolest. LDL (PJK-)* Kolest.LDL (PJK+)*

110-159 4 - 5.9% < 200 < 130 < 100

160-199 6 –   – 8 8% 200-239 130-159 100-129

> 200 > 8% > 240 > 160 > 130

Trigliserida (PJK-)* Trigliserida (PJK+)*

< 200 < 150

200-249 150-199

> 250 > 200

* = diperik diperiksa sa tiap 3 hingga 6 bulan

 

Glycated Hemoglobin (HbA1c) 1 Glycated

 

PADA TIAP KUNJUNGAN HARUS DIPANTAU 

KGD Sewaktu



Tekanan darah (diukur dalam keadaan duduk)



Indeks Massa Tubuh = BB (kg) / TB (M)2

PEMERIKSAAN TD sistolik (mmHg) TD diastolik IMT Pria (Kg /M2) IMT wanita (Kg/M2)

BAIK < 130 < 80 20-24.9 18.5-22. 9

LUMAYAN 130-150 80-85 25- 27 23- 25

BURUK >150 >85 < 20 atau >27 < 18.5 atau >25

 

Tuj ujua uann Pen eng gel elol olaan aan Diabetes Mellitus 

Menghilangkan gejala



Mempertahankan rasa sehat



Memperbaiki kualitas hidup



Mencegah komplikasi (akut dan kronis)

 

Mengurangi laju komplikasi yang sudah ada Menurunkan jumlah kematian

 

MANAGEMENT OF DM 

Regular Blood Glucose Monitoring

  rug Therapy

  iet

Exercise

91  

The Ominous Octet of DM2 Islet -cell Decreased Incretin Effect Impaired Insulin Secretion

Increased Lipolysis

Islet a-cell

Increased Glucagon Secretion

Increased HGP

Increased Glucose Reabsorption

Neurotransmitter  Dysfunction

Decreased Glucose Uptake

DeFronzo RA. Banting Lecture 2008. “From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus.”  

Site & Mode of Action of OADs Site of action

MOA



Insulin secretion

 HGO production Slow CHO Digestion

 Peripheral insulin sensitivity

Agents Sulfonylureas Repaglinide Nateglinide Biguanides Glitazones glucos osid idas asee a- gluc inhibitors

Glitazones Biguanides

93

 Adapted from DeFronzo DeFronzo R. Ann Intern Med 1999;131:2 1999;131:281 81

www.drsarma.in

 

Sites of Action of Currently Av Available Therapeutic Options ADIPOSE TISSUE

LIVER

MUSCLE

PANCREAS GLUCOSE PRODUCTION Metformin Thiazolidinediones

PERIPHERAL GLUCOSE UPTAKE

INSULIN SECRETION Thiazolidinediones Metformin Sulfonylureas: Glyburide, Gliclazide, INTESTINE Glimepiride Non-SU Secretagogues: Repaglinide, Nateglinide GLUCOSE ABSORPTION

Alpha-glucosidase inhibitors

 

Current Therapeuti Therapeuticc Targets Targets BRAIN

PANCREA S

Dopamine Analogs Pramlintide

GI TRACT

Insulin GLP-1 Agonists DPP-4 Inhibitors Sulfonylureas Pramlin Pram lintid tide e (α cells only) Meglitinides

?? KIDNEY ??

LIVER

Metformin Thiazolidin Thiazo lidinedion ediones es (TZD)

MUSCLE/FAT

GLP-1 Agonists Alpha Glucosidase Inhibitors

Metformin Thiazolidinediones (TZD)

 

SU’S: Mechanism of actio actionn

Others: •Dec glucagon Secretion •Extrapancreatic Binding to SU receptors in K channels

 

 Actions of Metformin Metformin

Dr.Sarma@works  

REPAGLINIDE: Mechanism of action

Meglitinides: have 2 common binding sites

w/ SU and 1 unique binding site

 

THIAZOLIDINEDIONES: MOA

 

PPAR-g activators Insulin sensitizers

LIVER, MUSCLE, FAT Activate insulin-responsive genes regulating - Glc Glc an and d llip ipid id me meta tab b

- Insulin Insulin s sign ignalli alling ng - Ad Adipoc ipocyt yte e diff differe erenti ntiati ation on

 

GLP-1 MIMETIC: EXENATIDE 

SC injections: absorbed equally from arm, abdomen, thigh



Peak: 2 hrs



Duration: up to 10 hrs

 

INHIBITORS DPP-IV INHIBITO RS

Sitagliptin

 

COMB COMBINA INATIO TION N PILLS PILLS AVAIL AILABL ABLEE

- imp impro rove ve com compli plianc ance e  



Gliben Gli bencla clamid mide e + Metfo Metformin rmin (Gluco (Glucovvance) ance)



Glip Gl ipiz izid ide e + Metf Metform ormin in (N (Nor orsu sulilin) n)



Metformi Metf orminn + Rosi osigli glitaz tazon one e (Av (Avandam andamet) et) Glim Gl imep epir irid ide e + Met Metfformin ormin (S (Sol olos osam amet et))



Sita Si tagl glip ipti tinn + Metf Metform ormin in (J (Jan anum umet et))



Pioglitazone: Metformin ( ActosMet)



 

Sejarah Insulin 



1921 Insulin ditemukan oleh Banting dan Best  1922 Leonard Thompson adalah pasien pertama yang mendapat suntikan insulin





 

1923 Novo Nordisk mulai produksi Insulin Hewan (Sapi dan Babi) 1973 Insulin Hewan Monokomponen 1987 1990

Insulin Human Insulin Analog

 

Insulin is Discov Discovered! ered! 

1921 –  1921  – Ontario Ontario Canada 

Frederick Banting and his assistant Charles Best administer canine pancreas extract extr act to a diabetic dog and keep it alive for 70 days.



1923 

Frederick Banting and J.J. Macleod win the Nobel Prize for Medicine for their

discovery of insulin.  

J. L. Age 3 yrs. Weight 15 lbs, December 15, 1922. Courtesy of of Eli Lilly and 29 Company Archives." "J. L. Weight lbs, February 15, /1923. Courtesy of of Eli Lilly and Company Archives

 

INDIKASI PENGGUNAAN INSULIN 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11.

DM tipe 1 Penurunan berat badan yg cepat Hiperglikemia yg berat disertai dg ketosis Ketoasidosis diabetik Hiperglikemia hiperosmolar non ketotik Hiperglikemia dg asidosis laktat Gagal dg kombinasi OAD dosis hampir max Stress berat Kehamilan dg DM atau DM Gestasional Gangguan fs. ginjal atau hati yg berat Kontraindikasi dan atau alergi thp OAD

 

KAPAN INSULIN DIPERLUKAN? Data UKPDS :  50% DMT2 perlu insulin setelah 6 tahun  Fungsi B-cell yg rendah pd saat diagnosis  risiko kegagalan OHO lebih tinggi Marre M. Int J Obesity (2002) ; 26 (Suppl 3) : S25 -S30 

 

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

HbA1c > 10 % 



FPG >260 mg/dl 



or

Symptomatic 



or

or

Ketotic

IMMEDIATE INSULIN

 

Modern "Aggressiv "Aggressive" e" Rx 4 

HbA1c not < 7% by 6 months

Start Insulin

 

INSULIN ANALOGS

Glu  Asn

Lys

RAPID-ACTING / ULTRASHORT-ACTING ULTRASHORT -ACTING INSULINS LONG-ACTING INSULINS

Insulin glulisine

 Alterations in pharmacokinetic properties  

Long-acting insulins 





Insulin analogs: 

Insulin glargine



Insulin detemir

Can’t be mixed with other insulins so need to use different syringes Used as BASAL insulin (fasting, between meals, overnight)

 

Insulin glargine

Absorption less variable day to da day y and not si site te nor dose dependent eakless ss insulin (b (broa road d plasma concentrati concentration on plateau) plateau)  Peakle  – IDEAL  –  IDEAL once daily (usually) basal insulin  Acidic pH (4.0) 

 

Insulin detemir Myristic acid

Thr removed at B30

 

Tip jangka e insulinwaktu berdakerjanya be sarkan pu:ncak dan 1.

Insu In suli linn ker kerja ja sa sang ngat at ce cepa patt : Nov NovoR oRap apid id, Humalog, 

2. 3. 4. 5.

Apidra Insu In suli linn ke kerrja pe pend nde ek : , Hum umul ulin in R Insu In suli linn ker kerja ja se sed dan angg : , Hu Humu muli linn N Insu In suli linn cam campu purr : , Hu Humu mulin lin 30 30/7 /70 0, Nov NovoM oMix ix 30, Hum umaalo logg 25 Insu In suli linn ker kerja ja pa panj njan angg : Le Leve vemi mirr, Lantus

 

Kendala Terapi Insulin Adanya anggapan :   

  

Sekali dimulai, tidak pernah bisa berhenti Akan membatasi aktivitas sehari-hari Memulai terapi Insulin berarti: Saya telah gagal DM-nya sudah menjadi serius Suntikan insulin akan sangat sakit/nyeri Suntikan insulin menyebabkan kebutaan Frank’s story : “Jika anda tidak bekerja keras, anda akan saya suntik insulin lho”

 

Prinsip Terapi 





Insulin Basal    menurunkan gula darah puasa Insulin Bolus    menurunkan gula darah  post prandial  prandial (setelah makan) Insulin Premixed    menurunkan GD puasa dan GD 2 jam PP

 

Macam-macam Rejimen Insulin 

Basal Bolus

4 suntikan per hari (3 bolus dan 1 basal) 



Satu kali suntikan insulin basal pada malam hari ditambah dengan obat oral Premixed Insulin, sekali sampai 3 kali sehari, sebelum makan.



Premixed  dikombinasi dengan short acting acting

 

4 Suntikan per Hari 3 Short + 1 Intermediate/Long Acting (Basal Bolus)

6

7

8

time

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

 

Dua kali Suntikan Premix  Premixed ed Insulin Insulin Per Hari

6

7

8 time

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

 

Tempat Penyuntikan Insulin Subkutan : Searah Jarum Jam

75 -90

1 -15

61 -75

16 -30

45 -60

31 -45

 

Contin tinuou uouss IV ins insuli ulinn infu infusio sionn Con 

Used to maintain glycemic control in hospitalized patients with high blood glucose levels; in DKA and HHNS



Regular Re gular insulin may be used IV





May also be given preoperatively or postoperatively More frequent BS monitoring ( q1-2 hours per agency protocol)

 

Efek Samping Insulin 



Hipoglikemia (kadar glukosa darah terlalu rendah)



Peningkatan berat badan Reaksi Alergi (kemerahan, gatal-gatal di tempat penyuntikkan)



Lipodistrofi

 

DIABETES DAN PERAN INSULIN DALAM PENANGANANNY PENANGANANNYA A

Dr. SUHAEMI, SpPD, FINASIM  

Insulin is Discov Discovered! ered! 

1921 –  1921  – Ontario Ontario Canada 

Frederick Banting and his assistant Charles Best administer canine pancreas extract extr act to a diabetic dog and keep it alive for 70 days.



1923 

Frederick Banting and J.J. Macleod win the Nobel Prize for Medicine for their

discovery of insulin.  

J. L. Age 3 yrs. Weight 15 lbs, December 15, 1922. Courtesy of of Eli Lilly and Company Archives." / "J. L. Weight 29 lbs, February 15, 1923. Courtesy of of Eli Lilly and Company Archives

 

Leonard Thompson

1922

–

1923

Meninggal tahun 1935

 



1969 



Ames Diagnostics releases the first portable glucose meter

1979 

First insulin pump marketed



First Hba1c test devised

 

Perkembangan Terakhir Injeksi Insulin

 

Insulin Delivery Devices 3

 

Inhaled Insulin 

Exubera

 

Inhaled Insulin 1-1-08 voluntary discontinuation 4-6-08 Cancer Warning

 

Exubera (Inhaled Insulin)

Insulin Blisters

for Aerosol www.drsarma.in

136

 

Ot Othe herr Inj Injec ecta tabl ble e Dru Drugs gs 1 

Exenatide (Byetta) 

insulin secretagogue  peptide 

gila monster saliva



use with other drugs



no hypoglycemia



bid

 

Exenatide (Byetta)

www.drsarma.in

138

 

Bolus Wizard Calculator : meter-entered

Paradigm 512™ Paradigm Link™





Monitor sends BG value to pump via radio waves : No transcribing error Enter carbohydrate intake into pump



“Bolus Wizard” calculates suggeste su ggested d dose

 

Smart Insulin Pumps

 

CGMS

 

More New Tec Technology hnology

 

SMBG 

Value in Type 2 DM



not established Useful for titrating insulin

 

Gly Glycated cated Hemoglobin (HbA1c) 2

 

Insulin 

Acute Complication: Hypoglycemia



Tx: (15/15 or 20/20 Rule)

Give 15/20 g simple carb and recheck

c

c

c

BG in 15/20 minutes

 

Insulin – Acute Insulin –  Acute Complication Hypoglycemia

 

How to prevention Complications Complication s of Diabetes ? 1.

Weight reduction, Exercise

2.

Strict control hyperglycemia

4.

Achieving lipid profile targets Smoki Sm oking ng ce cessa ssati tion on

5.

Rx. of Hypertension with ACEi/ ARB

6.

Low dose dose aaspir spirin in the therap rapy y

7.

Statin Sta tin therapy therapy for for all T2DM T2DM

8.

ACEii or ARB for al ACE alll wit with h MAU

9.

Early detection and evaluation

3.

www.drsarma.in

148

 

AACE/ACE Diabetes Algorithm for Gly Glycem cemic ic Con Contr trol ol

American Association of Clinical Endocrinologists. AACE/ACE Diabetes Algorithm for for Glycemic Control. Available at https://www.aace.com/publications. https://www.aace.com/publications.  

KRITERIA PENGENDALIAN DM Konsensus PERKENI 2006

BAIK

SEDANG

BURUK

Gula Darah Puasa

80 - 100

100 10 0 - 12 125 5

> 126

Gula Darah 2 JSM

80 - 14 144 4

145 14 5 - 17 179 9

> 180

HbA1C (%)

< 6,5

6.5 - 8

>8

Kolesterol Koleste rol Total Total

< 200

200 20 0 - 23 239 9

> 240

Kolesterol LDL

< 100

100 10 0 - 12 129 9

> 130

Kolesterol HDL

> 45

Trigliserida

< 150

150 15 0 - 19 199 9

> 200