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 : 14-05-2008Pekerjaan:• 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 FASTINGBG/mg%

POSTPRANDIALBG/mg%

RANDOMBG/mg%

NODIABETES

80 - <110 80 - <140 80 - <140

PREDIABETES

110 - 125 140 - 199

DIABETES ≥ 126 ≥ 200 ≥ 200

Prinsip Dasar Terapi Diabetes Mellitus

1

PENGATURAN MAKAN

2

LATIHANJASMANI

OBAT HIPOGLIKEMIK

4

3

PENYULUHAN

CANGKOK PANKREAS

5

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

1%

Hasil dari UKPDS: Kontrol yang baik pada DM T2 mampu menurunkan resiko

komplikasi

Kematian karena diabetes

Infark miokard

Komplikasi mikrovaskuler

Gangguan pembuluh darah perifer

‐21%

‐14%

‐37%

‐43%

Menurunkan resiko*Penurunan 1% HbA1c

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

Stratton IM et al. BMJ 2000;321:405–412

PRINSIP PENGOBATAN DIETKebutuhan 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

6.30 9.30 12.00 15.00 19.00 21.00

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

PRINSIP OLAHRAGA PADA DIABETES

Pilih olahraga yang disenangi

Melibatkan otot-otot besarFrekuensi : 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

RythmisInterval

ProgresifEndurance

Treatment options for type 2 diabetes

• Sulfonylureas– 1st generation e.g. chlorpropamide,

tolbutamide– 2nd generation e.g. glyburide,

gliclazide, glipizide, gliquidone– 3rd generation e.g. glimepiride– Modified release

• Glinides/meglitinides– Non-sulfonylureic e.g. repaglinide– Amino acid derivatives e.g. nateglinide

• Biguanides– e.g. metformin

• Thiazolidinediones– e.g. rosiglitazone, pioglitazone

• α-glucosidase inhibitors– e.g. acarbose

• Insulin– regular– intermediate/long acting– pre-mixed– analogs

• rapid acting• long acting

• Fixed-dose oral antidiabetic drug combinations– e.g. glyburide/metformin,

glipizide/metformin, rosiglitazone/metformin

MetforminHow it works • Decreases hepatic glucose output

• Lowers fasting glycemiaExpected HbA1creduction

~ 1.5%

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.

SulfonylureasHow they work Enhance insulin secretion

Expected HbA1creduction

~ 1.5%

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 SECRETIONSulfonylurea Length of

actionBegins ofaction

Daily dose(mg)

Route of 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

GlinidesHow they work Stimulate insulin secretion (but

differently from sulfonylureas)Expected HbA1creduction

~ 1.5% (repaglinide)

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 InhibitorsHow they work Inhibit degradation of endogenous

GLP-1

Expected HbA1creduction

~0.8%

Adverse events Minimal

Weight effects Neutral

CV effects Unknown

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

α-Glucosidase InhibitorsHow they work ↓ rate of digestion of polysaccharides in

proximal small intestine (primarily lowering PPG levels without causing hypoglycemia)

Expected HbA1creduction

0.5–0.8%

Adverse events • Increased gas production • GI symptoms

Weight effects Weight neutralCV 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 HbA1creduction

0.5–1.4%

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 HbA1creduction

0.5–1%

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 InhibitorsHow they work Inhibit degradation of endogenous

GLP-1

Expected HbA1creduction

~0.8%

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 HbA1creduction

0.5–0.7%

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.

InsulinHow it works Direct compensation for lack of

insulin sensitivityExpected HbA1creduction

1.5–2.5%

Adverse events Hypoglycemia

Weight effects Weight gain of ~ 2–4 kgCV 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

Years From Diagnosis

T2 DMphase I

T2 DMphase II

Stages of Type 2 Diabetes

Lebovitz, 2000

T2 DM phase III

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

100

75

50

25

0

Beta CellFunction

(%)IGT Postpandrial

Hiperglycemi T-2 DM phase IBeta Cell function

± 50 %

25

Summary: Expected HbA1c ReductionIntervention 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 than nateglinide Adapted from Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

Factors that May Affect ComplianceWeight Gain

GI Side Effects

2-3x Daily Dosing

Insulin – intermediate/long XInsulin – short/rapid X XMetformin X XSulfonylurea XGlinides X XTZDs Xα-Glucosidase inhibitors X XGLP-1 agonist X XPramlintide X XDPP-IV inhibitors

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

Which second-line therapy?HbA1C

Pros Cons

SU 1.5 Large clinical database, inexpensive Weight gain and hypoglycaemia

TZD 0.5–1.4 No hypoglycaemia, some benefits on

lipids

Oedema, heart failure, weight gain,

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

Years From Diagnosis

T2 DMphase I

T2 DMphase II

Stages of Type 2 Diabetes

Lebovitz, 2000

T2 DM phase III

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

100

75

50

25

0

Beta CellFunction

(%)IGT Postpandrial

Hiperglycemi T-2 DM phase IBeta Cell function

± 50 %

29

Effectiveness of Type 2 Diabetes Therapy

Diet & Exercise 1% <7%

TZDAlpha-glucosidase

Inhibitors

Metformin Insulin

Secretagogues

1.5-2%

1-1.5%<8%

CombinationOral

Agents3-4% <8-10%

Insulin 5% ormore >10%

Starting HbA1c

Klasifikasi InsulinKelas Mulai efek Puncak Lama Aksi pendekActrapid, Humulin R

15-30 mnt 2-4jam 6-8jamCampuran (premixed)Humulin 30/70,Mixtard 30/70

60 mnt 1-8jam 14-15 jamAksi sedangHumulin N, Insulatard

2-4jam 1-8jam 14-15 jam

Aksi panjangLantus , Levemir

Tanpa Puncak 24 jam

What are the reasons for the shortcomings of insulin?

Subcutaneoustissue

Mol/l

Diffusion

Capillarymembrane

10‐3 10‐4 10‐5 10‐8

Adapted from Brange J et al. Diabetes Care 1990;13:923

Dissociation in subcutaneous tissue

That has to dissolve in SC fluids and dissociate into monomers……..

32

Klasifikasi Insulin yang baruKelas Mulai efek Puncak Lama Aksi cepat (analog)Lyspro (Humalog)Aspart (Novo Rapid)Apiora

5-15 mnt 2 jam 4-6jam

Campuran (premixed)Humalog Mix 25/75Novomix 30/70

5-15mnt 2-4jam 12-14 jam

LOKASI PENYUNTIKKAN

35

Insulin Regimen Evolution

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

Insulin > Cara pemberian insulin > Semprit dan jarum

Dahulu:Agar tidak salah dosis,kemasan insulin40U/ml atau 100U/mldisesuaikan denganskala pada spuit,bisa 40 atau 100

Sekarang: ?Tidak tersedia lagi

38

NovoPen®

39

40

Sistem NovoLet®

INSULIN ANALOG: 1.NovoRapid2.NovoMix3.Levemir

45

Summary: Expected HbA1c ReductionIntervention 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 than nateglinide Adapted from Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

Factors that May Affect ComplianceWeight Gain

GI Side Effects

2-3x Daily Dosing

Insulin – intermediate/long XInsulin – short/rapid X XMetformin X XSulfonylurea XGlinides X XTZDs Xα-Glucosidase inhibitors X XGLP-1 agonist X XPramlintide X XDPP-IV inhibitors

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

48

ADA/EASD consensus algorithm

At diagnosis:Lifestyle + Metformin

Lifestyle + Metformin+ Basal insulin

Lifestyle + Metformin+ Sulfonylurea

Lifestyle + Metformin+ Intensive insulin

Tier 1:well-validated therapies

STEP 1 STEP 2 STEP 3

Call to action if HbA1c is ≥7%

Tier 2:Less well validated therapies

Lifestyle + Metformin+ PioglitazoneNo hypoglycaemiaOedema/CHFBone loss

Lifestyle + Metformin+ Pioglitazone+ Sulfonylurea

Lifestyle + metformin+ Basal insulin

Lifestyle + metformin+ GLP-1 agonistNo hypoglycaemiaWeight lossNausea/vomiting

Nathan DM, et al. Diabetes Care 2009;32 193-203.

49

DM tipe 1

1980

1980 2009