Tatalaksana dan Titrasi

Insulin
RSUD Balangan
dr. Riswanto, SpPD
 Diabetes 2003-2025 Epidemiology Projections
An increasing problem worldwide
World
2003 = 194 M
2025 = 333 M
NA
EUR
↑ 72%
23.0 M
36.2 M 48.4 M
58.6 M EMME
↑57.0% SEA
↑21% 19.2 M WP
39.4 M 39.3 M
↑105% 81.6 M 43.0 M
↑108% 75.8 M
↑79%
SACA
AFR
14.2 M
26.2 M 7.1M
15.0 M
↑85%
↑111%

M = million, AFR = Africa, NA = North America, EUR = Europe,

SACA = South and Central America,
EMME = Eastern Mediterranean and Middle East,
SEA = South-East Asia, WP = Western Pacific
Diabetes Atlas Committee. Diabetes Atlas 2nd Edition: IDF 2003. 2
Islet Cell of Pancreas

3
 PANCREATIC ISLET MORPHOLOGY

β-Cells
(insulin) α-Cells
(glucagon)

NORMAL PANCREAS
Adapted from Rhodes CJ. Science. 2005; 307:380–384
Roles of Insulin and Glucagon in Normal Glucose
Homeostasis

+ –
Insulin* Glucose Glucagon*
(plasma concentration) (plasma concentration) (plasma concentration)
– +

*Insulin and glucagon secretion are also influenced by other nutrients, hormones, and neural input
Adapted from Berne RM, Levy MN, eds. Physiology. St. Louis, Mo: Mosby, Inc; 1998: 822–847.
5
PANCREATIC ISLET MORPHOLOGY: STRUCTURAL
DEFECTS ARE EVIDENT IN TYPE 2 DM

Normal T2DM

β-Cells Amyloid
(insulin) plaque

α-Cells
(glucagon)

• Disorganized and misshapen

THE PANCREAS IN TYPE 2
• Marked reduction in β-cell number
DIABETES • Amyloid deposit

T2DM = type 2 diabetes mellitus

Adapted from Rhodes CJ. Science. 2005; 307:380–384
Sekresi Insulin Kepekaan terhadap Insulin

50 % DM-2 50 %

Pre-Diabetes
70 - 100 % Gangguan Toleransi Glukosa 50 %

150 % Gangguan Metabolisme Glukosa 70 %

100 % Metabolisme Glukosa Normal 100 %

Riwayat Alami Diabetes Mellitus tipe-2

Kontribusi kadar glukosa puasa dan glukosa
prandial terhadap HbA1c

Kontribusi kadar glukosa prandial

Kontribusi terhadap HbA1c 30%
40%
45%
50%
70%
70%

60%

55%
50%

30%
Kontribusi kadar glukosa puasa

< 7.3 7.4-8.4 8.5-9.2 9.3-10.2 >10,3

Kuantil HbA1c
Monnier L et al. Diabetes Care 2003
Both fasting and postprandial hyperglycaemia
contribute to overall hyperglycaemia

15
Postprandial
hyperglycaemia
Blood glucose (mmol/l)

10 Fasting
hyperglycaemia Diabetes profile

5
Healthy profile

0
06:00 12:00 18:00 24:00 06:00
Time of day

Riddle M. Diabetes Care 1990;13:676−86.

 Well – validated Lifestyle
core therapies + Lifestyle
Metformin +
Metformin
+ +
At diagnosis : Basal insulin Intensive insulin
Lifestyle
Lifestyle
+ +
Metformin Metformin
+
Sulfonilurea
Step 1 Step 2 Step 3

Less – validated
Lifestyle
core therapies + Lifestyle
Metformin +
+ Metformin
Pioglitazon +
(No hypogycemia, Pioglitazone
Oedema/ CHF +
Bone loss ) Sulfonilurea
Lifestyle
+ Lifestyle
Metformin +
+
GLP-1 agonist Metformin
(No hypogycemia, +
Weight loss Basal insulin
Nausea /vomiting)

Algorythm for Metabolic management Type -2 Diabetes

Penatalaksanaan DM
1 2

3 4
Penemuan
insulin
 Diabetes
Devices
Pipeline
- past,
Advisory
present
Board
and
Meeting
future 18-19 March-2011
March 2009 Slide no 16

Historical steps in Novo Nordisk’s insulin

development
New Generation
Insulin Analogs

Basal
Insulin Analogs
Advancements

Biphasic
Insulin Analogs

Rapid-acting
Insulin Analogs
2000s
Recombinant
Human
Animal Insulin
Isolation
Insulin
of Insulin
(Banting & Best) Preparations
1990s

1977

1922
Time
 ( Program Insulin )
dosis =BBx0,5
60%rapid : 40% basal

Menjelang Menjelang Menjelang Menjelang

Makan Pagi Makan Siang Makan Malam Tidur Malam
20% 20% 20% 40%
Rapid-Acting Rapid-Acting Rapid-Acting Extended
Long acting

Menekan Mengendalikan
Hiperglikemi Post Prandial Glukosa darah
Basal
Memacu glikogenesis
Menekan Hepatic
Glucose Production
 Diabetes Pipeline Advisory Board Meeting 18-19 March 2009

Jika GDP yang tinggi mulai basal insulin

jika GDP dan 2j PP yang tinggi mulai dengan

premix atau tambahkan basal dengan OAD atau
mulai basal bolus
 Diabetes Pipeline Advisory Board Meeting 18-19 March 2009

Titrasi basal bolus insulin

GDP basal titrasi

• <70mg/dl kurangi 2 unit
• Basal insulin • 70-130mg/dl maintanace dose
• 130-180 mg/dl naikkan 2u tiap 3hari
• >180mg/dl naikkan 4u tiap 3 hari
• Cek HbA1C /3bln

GD 2j PP titrasi
• Fast acting Mulai 4u /hari naikkan 2u sampai
target tercapai tiap
3hari
OAD stop begitu start insulin rapid
 Diabetes Pipeline Advisory Board Meeting 18-19 March 2009

Titrasi premix insulin

GD sblm mkn pagi titrasi premix

<72 mg/dl kurangi 4u

Premix 72-126mg/dl tetap
Insulin 126-144mg/dl naikkan 2u
>144mg/dl naikkan 4u

Monitor GDP dan Gd2 j PP selama titrasi

 Diabetes Pipeline Advisory Board Meeting 18-19 March 2009

Analogue Insulin:
ANALOG INSULIN
for better physiologic, efficacy, safety and flexibility

NovoRapid – Rapid Acting

Analog

NovoMix – Premix
Analog

Levemir – Long Acting Analog

 Diabetes Pipeline Advisory Board Meeting 18-19 March 2009

---- Insulin endogen

Levemir

---- NovoRapid

NovoMix

Breakfast Lunch Dinner Bed time

 Limitation of Reguler & Premix HI
Period of unwanted
hyperglycemia
Normal insulin secretion
at mealtime
Change in serum insulin

Human insulin

Period of unwanted
hypoglycemia

Baseline
inflexibility injection time
level

Time (h)
SC injection
Injection Site Rotation
Pen Injection Technique
Injection Techniques
 Kriteria Pengendalian DM

Baik Sedang Buruk

1. Glukosa darah Puasa 80 – 109 110 – 125  126
2. Glukosa darah 2 jam 80 – 144 145 – 179  180
3. A1C (%) < 6,5 6,5 – 8 >8
4. Kolesterol total (mg/dl) < 200 200 – 239  240
5. Kolesterol LDL (mg/dl) < 100 100 – 129  130
6. Kolesterol HDL (mg/dl) > 45
7. Trigliserida < 150 150 – 199  200
8. IMT (kg/m2) 18,5–22,9 23 – 25  25
9. Tekanan darah (mmHg) < 130/80 130-140/80-90 >140/90
Guidelines provide HbA1c, independent FBG and PPBG
targets

Healthy ADA1 AACE3 IDF4 ADA/

EASD5

HbA1c* (%) <6.01 <7.0† 6.5 <6.5 <7.0†

FBG, mg/dl <100 90130 110 <110 70−130

(mmol/l) (<5.5)2 (5.07.2) (6.0) (<6.0) (3.9−7.2)

PPBG, mg/dl <140 <180 140 <145 <180

(mmol/l) (<7.8)**1 (<10.0)** (7.8)** (<8.0)** (<10.0)*
*
*DCCT referenced assays: normal range 4–6%; **1–2 hours postprandial; †ADA and ADA/EASD guidelines recommend
HbA1c levels as close to normal (<6%) as possible without significant hypoglycaemia1,5
AACE=American Association of Clinical Endocrinologists; ADA=American Diabetes Association;
EASD=European Association for the Study of Diabetes; IDF=International Diabetes Federation
1. ADA. Diabetes Care 2006;29(suppl 1):S4–S42.
2. ADA. Diabetes Care 2006;29(suppl 1):S43–8.
3. AACE. Endocr Pract 2002;8(suppl 1):40–82.
4. IDF. Global Guideline for Type 2 Diabetes. Brussels: International Diabetes Federation, 2005.
http://www.idf.org/webdata/docs/IDF%20GGT2D.pdf.
5. Nathan DM, et al. Diabetologia 2006;49:1711–21.
Type 2 Diabetes Mellitus Complications

MICROVASCULAR MACROVASCULAR
Retinopathy,
glaucoma or Cerebrovascular
cataracts disease

Cardiomyopathy Coronary
heart
Nephropathy disease

Peripheral
Neuropathy vascular
disease

Erectile dysfunction
Kaki Diabetes
Neuropati
Vaskular Manifestasi Neuropati Diabetik
Infeksi Sangat bervariasi
Kesemutan, baal, kebas, hilang rasa
sering tidak terhiraukan
MERUPAKAN RISIKO TERJADINYA
ULKUS, KARENA SENSASI NYERI
TIDAK ADA
Nyeri (Painful Neuropathy)