CV: dr.

R Bowo Pramono SpPD KEMD

• Lahir TEGAL 27-jan 1959
• Istri: dr. Astuti SpS, 2 putri
• Dokter Umum: FK UGM
• 17-01-1985
• SPPD : FK UGM 24-11-1997
• KEMD : 14-05-2008
Pekerjaan:
• 1987-2002 PKM Kedung Waringin Bekasi
• 1999-2004 RSU Selong Lombok Timur
• 2004-2010 RS DR Sardjito/FK UGM
• 2006-2013 Sekretaris Bagian Penyakit Dalam FK UGM
• 2007-2011 Sekretaris PAPDI Cabang Yogyakarta

1
DIAGNOSIS & MANAJEMEN
DM TIPE 2
 DIAGNOSIS:
DIAGNOSED FASTING POST RANDOM
BG/mg% PRANDIAL BG/mg%
BG/mg%
NO 80 - <110 80 - <140 80 - <140
DIABETES

PRE 110 - 125 140 - 199

DIABETES

DIABETES ≥ 126 ≥ 200 ≥ 200

Prinsip Dasar Terapi Diabetes Mellitus

1 2 3

PENGATURAN LATIHAN PENYULUHAN

MAKAN JASMANI

4 5

OBAT HIPOGLIKEMIK CANGKOK PANKREAS

Correlation between HbA1c level and mean
plasma glucosa levels on multiple testing
over 2-3 months

HbA1c Mean plasma glucose (mg/dL)

6 135
7 170
8 205
9 240
10 275
11 310
12 345

6
 Hasil dari UKPDS:
Kontrol yang baik pada DM T2 mampu menurunkan resiko
komplikasi
Penurunan 1% HbA1c Menurunkan resiko*

Kematian karena diabetes ‐21%

Infark miokard ‐14%

1%
‐37%
Komplikasi mikrovaskuler

Gangguan pembuluh darah perifer ‐43%

*p<0.0001 n=3,642 type 2 diabetes patients

Stratton IM et al. BMJ 2000;321:405–412
PRINSIP PENGOBATAN DIET
Kebutuhan kalori sesuai : kelamin,
umur , berat badan, aktifitas fisik,
pekerjaan, kehamilan, menyusui,
komplikasi
3 kali makan utama dan 3 kali makan
kecil
Jumlah dan waktu makan harus tepat
 JADWAL MAKAN DIABETES

Komposisi diet: 60-70 % hidrat arang

20-25 % lemak
10-15 % protein

20% 10% 25% 10% 25% 10%

6.30 9.30 12.00 15.00 19.00 21.00

PRINSIP OLAHRAGA PADA
DIABETES
Pilih olahraga yang disenangi
Melibatkan otot-otot besar
Frekuensi : Teratur 3-5 kali perminggu
Intensitas : Ringan sampai sedang
Durasi : 30 –60 menit / 5 X30 menit /minggu
Tipe : Aerobik (jalan, joging, ber sepeda)
Program Latihan
• Teratur (3-4 kali seminggu)
• 20- 40 menit didahului
pemanasan 5-10 mnt dan
cool-down 10 mnt
• CRIPE:
Continous
Rythmis
Interval
Progresif
Endurance
 Treatment options for type 2
diabetes
• Sulfonylureas • α-glucosidase inhibitors
– 1st generation e.g. chlorpropamide, – e.g. acarbose
tolbutamide
– 2nd generation e.g. glyburide, • Insulin
gliclazide, glipizide, gliquidone – regular
– 3rd generation e.g. glimepiride – intermediate/long acting
– Modified release – pre-mixed
– analogs
• Glinides/meglitinides • rapid acting
– Non-sulfonylureic e.g. repaglinide • long acting
– Amino acid derivatives e.g. nateglinide
• Fixed-dose oral antidiabetic
• Biguanides drug combinations
– e.g. metformin – e.g. glyburide/metformin,
glipizide/metformin,
rosiglitazone/metformin
• Thiazolidinediones
– e.g. rosiglitazone, pioglitazone
 Metformin
How it works • Decreases hepatic glucose output
• Lowers fasting glycemia
Expected HbA1c ~ 1.5%
reduction
Adverse events • GI side effects
• Lactic acidosis (quite rare)
Weight effects Weight stability or modest weight loss
CV effects Unconfirmed beneficial effect
demonstrated in UKPDS

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

 Sulfonylureas
How they work Enhance insulin secretion

Expected HbA1c ~ 1.5%

reduction
Adverse events Hypoglycemia (but severe episodes
are infrequent)
Weight effects ~ 2 kg weight gain common when
therapy initiated
CV effects UGDP suggested potential cause of
increased CVD mortality; not
substantiated by UKPDS

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

 INCREASED INSULIN SECRETION
Sulfonylurea Length of Begins of Daily dose Route of
action action (mg) excretion
Glibenclamide 16 – 24h 2 – 4h 1,25 – 15 R = 50%, B = 50%
Gliclazide 10 – 24h 2 – 4h 40 – 320 R = 70%, B = 30%
Glipizide 6 – 24h 2 – 4h 2,5 – 40 R = 80%, B =20%
Chlorpramide 24 – 72h 2 – 4h 100 – 500 Renal
Tolbutamide 6 – 10h 2 – 4h 100 – 1000 Renal
Glimepiride 24h 2 – 4h 1-6 R = 40%, B =60%
gliquidon 18 - 24h 2 - 4h 30 - 120 R = 5%, B = 95%

15
 Glinides
How they work Stimulate insulin secretion (but
differently from sulfonylureas)
Expected HbA1c ~ 1.5% (repaglinide)
reduction
Adverse events Hypoglycemia (may be less frequent
than some sulfonylureas)
Weight effects ~ 2 kg weight gain common when
therapy initiated
CV effects None mentioned in ADA
recommendations

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

Dipeptidyl Peptidase IV Inhibitors
How they work Inhibit degradation of endogenous
GLP-1

Expected HbA1c ~0.8%

reduction
Adverse events Minimal
Weight effects Neutral

CV effects Unknown

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

 α-Glucosidase Inhibitors
How they work ↓ rate of digestion of polysaccharides in
proximal small intestine (primarily lowering
PPG levels without causing hypoglycemia)

Expected HbA1c 0.5–0.8%

reduction
Adverse events • Increased gas production
• GI symptoms
Weight effects Weight neutral
CV effects Unconfirmed report of reduction of
severe outcomes in one clinical trial

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

 Thiazolidinediones
How they work Increase sensitivity of muscle, fat, and liver to
endogenous and exogenous insulin

Expected HbA1c 0.5–1.4%

reduction
Adverse events Weight gain and fluid retention

Weight effects • Increase in subcutaneous adiposity

• Redistribution from visceral deposits

CV effects • New / worsened CHF or peripheral edema

(due to fluid retention)
• Reduction in some secondary CV endpoints
demonstrated in PROactive study

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

 Glucagon-like Peptide 1 Agonist
(exenatide)
How it works Stimulates insulin secretion
Expected HbA1c 0.5–1%
reduction
Adverse events GI side effects (nausea, vomiting,
diarrhea)
Weight effects Weight loss of ~ 2–3 kg over 6 months
(may be result of GI effects)
CV effects None mentioned in ADA
recommendations

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

Dipeptidyl Peptidase IV Inhibitors
How they work Inhibit degradation of endogenous
GLP-1

Expected HbA1c ~0.8%

reduction
Adverse events Minimal
Weight effects Neutral

CV effects Unknown

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

 Amylin Agonists (pramlintide)
How it works Synthetic amylin analogue that inhibits
glucagon production in a glucose-
dependant fashion
Expected HbA1c 0.5–0.7%
reduction
Adverse events GI effects (nausea)
Weight effects Weight loss ~ 1–1.5 kg over 6 months
(may be due to GI effects)

CV effects None mentioned in ADA

recommendations

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

 Insulin
How it works Direct compensation for lack of
insulin sensitivity
Expected HbA1c 1.5–2.5%
reduction
Adverse events Hypoglycemia

Weight effects Weight gain of ~ 2–4 kg

CV effects • Beneficial effect on TG and HDL
• Weight gain may have an adverse
effect on CV risks

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

 Indikasi terapi Insulin:
• DM tipe 1
• DM tipe 2 yang tidak terkontrol diet, olah raga,
OHO.
• DM gestasional
• Gangguan faal hati & ginjal yang berat.
• Dengan infeksi akut (selulitis, gangren), TBC
berat, penyakit kritis (stroke/AMI)
• Dengan KAD/HHS
• Dengan fraktur atau pembedahan mayor
• Kurus (BB rendah), terkait malnutrisi (DMTM)
• Dengan penyakit Grave’s
• Dengan tumor ganas
• Dengan pemberian kortikosteroid
 100
Stages of Type 2 Diabetes

75
Beta Cell
Function Postpandrial
IGT T-2 DM phase I
(%) Hiperglycemi
50
Beta Cell function
± 50 %
T2 DM
phase I
25 T2 DM
phase II
T2 DM
phase III
0
-12 -10 -6 -2 0 2 6 10 14
Years From Diagnosis 25
Lebovitz, 2000
Summary: Expected HbA1c Reduction
Intervention Expected ↓ in HbA1c
Insulin 1.5 to 2.5%
Metformin 1.5%
Sulfonylureas 1.5%
Glinides 1 to 1.5%a
TZDs 0.5 to 1.4%
α-Glucosidase inhibitors 0.5 to 0.8%
GLP-1 agonist 0.5 to 1.0%
Pramlintide 0.5 to 1.0%
DPP-IV inhibitors ~0.8%
a Repaglinide is more effective
Adapted from Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
than nateglinide
Factors that May Affect Compliance
Weight GI Side 2-3x Daily
Gain Effects Dosing
Insulin – intermediate/long X
Insulin – short/rapid X X
Metformin X X
Sulfonylurea X
Glinides X X
TZDs X
α-Glucosidase inhibitors X X
GLP-1 agonist X X
Pramlintide X X
DPP-IV inhibitors

Adapted from Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

 Which second-line therapy?
ÐHbA1C Pros Cons
SU 1.5 Large clinical database, inexpensive Weight gain and hypoglycaemia

TZD 0.5–1.4 No hypoglycaemia, some benefits on Oedema, heart failure, weight gain,
lipids expensive
Insulin 1.5–3+ Large clinical database, most effective Hypoglycaemia, weight gain, need for
SMBG
AGI 0.5–0.8 No hypoglycaemia, weight neutral GI side-effects, expensive
GLP-1 analogue 0.5–1.0 No hypoglycaemia, weight loss GI side-effects, expensive, injected
Meglitinide 1.0–1.5 Fewer hypos than sulfonylurea TID dosing, expensive

SU: sulfonylurea; TZD: thiazolidinedione; AGI: α-glucosidase inhibitor

SMBG: self monitoring of blood glucose

ADA/EASD. Diabetes Care 2006; 29: 1963-1972, Diabetologia 2006; 49: 1711-21
 100
Stages of Type 2 Diabetes

75
Beta Cell
Function Postpandrial
IGT T-2 DM phase I
(%) Hiperglycemi
50
Beta Cell function
± 50 %
T2 DM
phase I
25 T2 DM
phase II
T2 DM
phase III
0
-12 -10 -6 -2 0 2 6 10 14
Years From Diagnosis 29
Lebovitz, 2000
 Effectiveness of Type 2 Diabetes Therapy
Starting HbA1c

Diet & 1% <7%

Exercise

1.5-2% Metformin TZD

Insulin Alpha-glucosidase <8%
Secretagogues Inhibitors 1-1.5%

Combination
Oral 3-4% <8-10%
Agents

Insulin 5% or more >10%

 Klasifikasi Insulin
Kelas Mulai efek Puncak Lama
Aksi pendek
15-30 mnt 2-4jam 6-8jam
Actrapid, Humulin R
Campuran (premixed)
60 mnt 1-8jam 14-15 jam
Humulin 30/70,Mixtard 30/70
Aksi sedang
2-4jam 1-8jam 14-15 jam
Humulin N, Insulatard

Aksi panjang
Tanpa Puncak 24 jam
Lantus , Levemir
 What are the reasons for the shortcomings of
insulin?
That has to dissolve in SC fluids and dissociate into monomers……..

Dissociation in subcutaneous tissue

Subcutaneoust
issue

Mol/l 10‐3 10‐4 10‐5 10‐8

Diffusion

Capillary
membrane

32
Adapted from Brange J et al. Diabetes Care 1990;13:923
 Klasifikasi Insulin yang baru
Kelas Mulai efek Puncak Lama
Aksi cepat (analog)
Lyspro (Humalog)
Aspart (Novo Rapid) 5-15 mnt 2 jam 4-6jam
Apiora

Campuran (premixed)
5-15mnt 2-4jam 12-14 jam
Humalog Mix 25/75
Novomix 30/70
LOKASI PENYUNTIKKAN
Insulin Regimen Evolution

35
Insulin > Cara pemberian insulin > Semprit dan jarum

Pemakaian semprit dan jarum memungkinkan Anda

untuk mengatur dosis dan membuat formulasi campuran
insulin. Keterbatasannya adalah membutuhkan
ketrampilan yang cukup untuk menarik dosis insulin
dengan tepat.
Cara menyuntik insulin
Dahulu:
Agar tidak salah dosis,
kemasan insulin
40U/ml atau 100U/ml
disesuaikan dengan
skala pada spuit,
bisa 40 atau 100

Sekarang: ?
Tidak tersedia lagi
38
NovoPen®

39
Sistem NovoLet®

40
INSULIN ANALOG:
1. NovoRapid
2. NovoMix
3. Levemir
45
Summary: Expected HbA1c Reduction
Intervention Expected ↓ in HbA1c
Insulin 1.5 to 2.5%
Metformin 1.5%
Sulfonylureas 1.5%
Glinides 1 to 1.5%a
TZDs 0.5 to 1.4%
α-Glucosidase inhibitors 0.5 to 0.8%
GLP-1 agonist 0.5 to 1.0%
Pramlintide 0.5 to 1.0%
DPP-IV inhibitors ~0.8%
a Repaglinide is more effective
Adapted from Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
than nateglinide
Factors that May Affect Compliance
Weight GI Side 2-3x Daily
Gain Effects Dosing
Insulin – intermediate/long X
Insulin – short/rapid X X
Metformin X X
Sulfonylurea X
Glinides X X
TZDs X
α-Glucosidase inhibitors X X
GLP-1 agonist X X
Pramlintide X X
DPP-IV inhibitors

Adapted from Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

 ADA/EASD consensus algorithm
Tier 1: Call to action if HbA1c is ≥7%
well-validated therapies
Lifestyle + Metformin Lifestyle + Metformin
+ Basal insulin + Intensive insulin
At diagnosis:
Lifestyle +
Metformin
Lifestyle + Metformin
+ Sulfonylurea

STEP 1 STEP 2 STEP 3

Tier 2:
Less well validated Lifestyle + Metformin
therapies + Pioglitazone Lifestyle + Metformin
No hypoglycaemia + Pioglitazone
Oedema/CHF + Sulfonylurea
Bone loss

Lifestyle + metformin
+ GLP-1 agonist Lifestyle + metformin
No hypoglycaemia + Basal insulin
Weight loss
Nausea/vomiting 48
Nathan DM, et al. Diabetes Care 2009;32 193-203.
DM tipe 1

49
1980
1980 2009