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Diabetes Mellitus 2017
Diabetes Mellitus 2017
Type 1 diabetes
β-cell destruction
Type 2 diabetes
Progressive insulin secretory defect
Other specific types of diabetes
Genetic defects in β-cell function, insulin action
Diseases of the exocrine pancreas
Drug- or chemical-induced
Gestational diabetes mellitus
¨ Complications :
- Stroke
- Heart attack
- Kidney disease
- Eye Disease
- Nerve Damage
Diabetes Mellitus
Type 1 Diabetes Type 2 Diabetes
- cells that produce insulin are - blood glucose levels rise due to
destroyed
- results in insulin dependence 1) Lack of insulin production
- commonly detected before 30 2) Insufficient insulin action
(resistant cells)
- commonly detected after 40
- effects > 90%
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 insulin-
dependent or juvenile-onset
diabetes
Cause is unknown, but likely
to have genetic, autoimmune
component
Diabetes Mellitus Type 2
Results from decreased
insulin sensitivity and
decreased pancreatic beta-
cell 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!
1986 NEJM “Stages” in Development of Type1Diabetes
(?Precipitating Event)
Genetic Overt
Predisposition immunologic
abnormalities Progressive
loss insulin
Beta cell mass
release
Normal insulin
release Overt
Glucose diabetes
normal
C-peptide
present
No
C-peptide
Age (years)
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
Environmental trigger
Incidence more common in fall and winter - viral infection trigger?
Possibly multiple potential triggers in early infancy: viruses, cows milk,
toxins
TLC Post-prandial
OAD glucose
Plasma ACEI
AIIA
glucose
Fasting glucose
0 10 20 30
Years of Diabetes
Adapted from International Diabetes Center (IDC). Minneapolis, Minnesota
RISKESDAS 2008
Total DM = 5,7%
Diagnosed DM = 1,5%
Undiagnosed DM = 4,2%
IGT = 10,2 % Undiagnosed patients
8 million >21
million
2000
2030
Epidemiology of Diabetes
Diabetes in the World
Year
31.7 2000 20.8
China
India 17.7
USA
8.4 6.8
Indonesia 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
Year
79.4 2030 42.3
China
India 30.3
USA
21.3 8.9
Indonesia Japan
millions
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?
TYPE 2 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 – Meals
Super Size
Each 12 oz soda has 10 tsp
sugar (150 cal)
One can of soda/day
child’s risk obesity 60%
Most popular Canadian
drink
> 110 L/ person/yr
1942-1998:
US production increased 9X
Maharaja Mac ? Jumbo Vadapav? Double
Cheese Pizza?
Single Therapy
15
13
11 Re tino p
9
RELATIVE Ne p h
7
RISK
5 Ne uro p
1
6 7 8 9 10 11 12
Mean A1C
Diminished
insulin
Hyperglycemia Muscle and fat
Liver
No Insulin
Patho-Cont.:DM Type 2
History of DM
Definisi :
Insulin adalah hormon yang
dikeluarkan oleh sel beta
pankreas yang berperanan
dalam mengatur kadar glukosa
darah
Tenaga
Glukosa dibakar
Pintu
tertutup
Tenaga
Insulin
plasma
FASE 1 FAS E - 2
Penderita DM tipe-2
Insulin with
Oral Hypo(s) or without
Life Style Monotherapy
Combination Oral Hypo
Glycemic agent
Beta Cell
Function
(%)
IGT Postprandial T2 DM T2DM phase III
Hyperglycemiaphase I T2DM
phase II
-12 –10 -6 -2 0 2 6 10 14
Years from Diagnosis
Lebovitz H. Diabetes Review 1999;7:139-53
Hyperglycemia
Antoxidants
Oxidative Sress
Vascular complications
Oxidative stress
Decreased
Incretin Effect Increased
Impaired Lipolysis
Insulin Secretion
Islet a-cell
Increased
HGP
Neurotransmitter Decreased Glucose
Dysfunction 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 – 1 : Endothelium
GLUT – 2 : Liver, B-cells of Pancreas
GLUT – 3 : Neurons
GLUT – 4 : Muscle, Adipose Tissue
GLUT – 5 : Intestine
Insulin Action
Insulin Glucose
transloca
t ion
Insulin
receptor
PPARg 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, 2 nd Ed.
Insulin Resistance
Insulin Glucose
Translocation
Insulin
receptor
X
X Synthesis GLUT 4
PPARg +RXR mRNA
PPRE transcription
promoter Coding reg
Muscle
Cells
Modified from Howard L. Foyt et al. Thiazolidinediones. Diabetes Mellitus: a Fundamental and Clinical Text, 2 nd Ed.
Physiological Serum Insulin Secretion Profile
50
25
Diabetic
nephropathy Diabetic
Leading cause of neuropathy
end-stage renal disease2 Leading cause of non-
traumatic lower
extremity amputations5
1
Fong DS, et al. Diabetes Care. 2003; 26 (Suppl. 1): S99–S102. 2Molitch ME, et al. Diabetes Care. 2003; 26 (Suppl. 1): S94–8.
3
Kannel WB, et al. Am Heart J. 1990; 120: 672–6. 4Gray RP & Yudkin JS. In Textbook of Diabetes 1997.
5
Mayfield JA, et al. Diabetes Care. 2003; 26 (Suppl. 1): S78–S79.
Chronic Complications-Microvascular :
1. Diabetic Retinopathy
Chronic Complications-Microvascular
2. Nephropathy
Chronic Complications-Microvascular
Gastroparesis
3. Diabetic Neuropathy
Clinical assessment
symptoms and signs
may be obvious or subtle
- history of rest pain at night
- gangrene
colour
- white
- red (hyperaemic skin)
temperature
- cool
Blood Vessel
Lumen
Chronic Complications-Microvascular
Sexual problems for men
erectile dysfunction
retrograde ejaculation
high
blood sugar level
liver
(90mg/100ml)
low
liver
triggers releases
hunger sugar pancreas
liver glucagon
GEJALA KLASIK DM
4P
1. POLI DIPSIA
2. POLIFAGIA
3. POLI URIA
3. PENURUNAN BERAT BADAN
Signs and Symptoms
Klinis Diabetes Melitus :
DM TIPE 1 DM TIPE 2
Mudah terjadi ketoasidosis Jarang ketoasidosis (HONK bisa)
Pengobatan harus dgn insulin Tidak mesti diberi insulin
Onsetnya akut Onsetlambat (pelan-pelan)
Biasanya kurus /Umur muda Gemuk atau tak gemuk / > 45 thn
Terkait dgn HLA-DR3 & DR4 Tak ada kaitan dengan HLA
ICA; GADA; & IAA selalu (+) Tak ada autoantibodi
Riwayat keluarga (+) pd 10% Riwayat keluarga (+) pada 30%
30-50% kembar identik terkena ± 100% kembar identik terkena
Kriteria Pemantauan Diabetes Mellitus
KGD Sewaktu
Tekanan darah (diukur dalam keadaan duduk)
Indeks Massa Tubuh = BB (kg) / TB (M)2
Exercise
91
The Ominous Octet of DM2
Islet b-cell
Decreased
Incretin Effect Increased
Impaired Lipolysis
Insulin Secretion
Islet a-cell
Increased
HGP
Neurotransmitter Decreased Glucose
Dysfunction 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 Agents
Sulfonylureas
Insulin Repaglinide
secretion
Nateglinide
HGO Biguanides
production Glitazones
PANCREAS
GLUCOSE
PRODUCTION PERIPHERAL
Metformin GLUCOSE
Thiazolidinediones UPTAKE
Insulin
GLP-1 Agonists
Dopamine Analogs DPP-4 Inhibitors Metformin
Pramlintide Sulfonylureas Thiazolidinediones
Pramlintide (α cells only) (TZD)
Meglitinides
GI TRACT MUSCLE/
?? KIDNEY ?? FAT
Metformin
GLP-1 Agonists Thiazolidinediones
Alpha Glucosidase (TZD)
Inhibitors
SU’S: Mechanism of action
Others:
• Dec glucagon
Secretion
• Binding to
Extrapancreatic
SU receptors
in K channels
Actions of Metformin
Dr.Sarma@works
REPAGLINIDE:
Mechanism of action
PPAR- activators
LIVER, MUSCLE, FAT
Insulin sensitizers Activate insulin-responsive genes
regulating
- Glc and lipid metab
- Insulin signalling
- Adipocyte differentiation
GLP-1 MIMETIC:
EXENATIDE
Sitagliptin
COMBINATION PILLS
AVAILABLE
- improve compliance
Glibenclamide + Metformin (Glucovance)
Glipizide + Metformin (Norsulin)
Metformin + Rosiglitazone (Avandamet)
Glimepiride + Metformin (Solosamet)
Sitagliptin + Metformin (Janumet)
Pioglitazone: Metformin ( ActosMet)
Sejarah Insulin
1921 Insulin ditemukan oleh
Banting dan Best
Data UKPDS :
50% DMT2 perlu insulin setelah 6
tahun
Fungsi B-cell yg rendah pd saat
diagnosis risiko kegagalan OHO
lebih tinggi
HbA1c > 10 %
IMMEDIAT
or
FPG >260 mg/dl
or
E INSULIN
Symptomatic
or
Ketotic
Modern "Aggressive" Rx 4
HbA1c not < 7% by 6
Start
months
Insulin
INSULIN ANALOGS
Glu
Asn
Lys
RAPID-ACTING /
ULTRASHORT-ACTING INSULINS LONG-ACTING INSULINS
Insulin glulisine
Basal Bolus
4 suntikan per hari (3 bolus dan 1 basal)
6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5
time
6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5
time
75 -90 1 -15
61 -75 16 -30
45 -60 31 -45
Continuous IV insulin infusion
Used to maintain glycemic control in
hospitalized patients with high blood
glucose levels; in DKA and HHNS
1922 – 1923
1979
First insulin pump marketed
1-1-08
voluntary discontinuation
4-6-08
Cancer Warning
Exubera (Inhaled Insulin)
Insulin Blisters
for Aerosol
www.drsarma.in 136
Other Injectable Drugs 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
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))) Paradigm 512™
Paradigm Link™
American Association of Clinical Endocrinologists. AACE/ACE Diabetes Algorithm for Glycemic Control.
Available at https://www.aace.com/publications.
KRITERIA PENGENDALIAN DM
Konsensus PERKENI 2006