Dr. PANDJI MOELJONO, Sp.PDSUBDEP PENYAKIT DALAM – FK. UNIV. HANG TUAH

RUMKITAL Dr. RAMELAN

Dr. PANDJI MOELJONO, Sp.PDSUBDEP PENYAKIT DALAM – FK. UNIV. HANG TUAH

RUMKITAL Dr. RAMELAN

Type 2 Diabetes Mellitus: The Disease and Its Management Type 2 Diabetes Mellitus:

The Disease and Its Management

90% NIDDM are closely related to OBESITY DIABESITY

Penderita DM 2010:

(Zimmet, International Congress of Endocrinology, Sydney 2000)

Asia : 111%

Dunia : 87%Dunia : 87%

DefinisiDefinisi

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemiaresulting from defects in insulin secretion, insulin action, or both (Expert Committee on the Diagnosis and Classification of Diabetes mellitus 2002)

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemiaresulting from defects in insulin secretion, insulin action, or both (Expert Committee on the Diagnosis and Classification of Diabetes mellitus 2002)

Long-term damage, dysfunction, and failure of various organs especially the eyes, kidneys,

nerves, heart, and blood vessels

Long-term damage, dysfunction, and failure of various organs especially the eyes, kidneys,

nerves, heart, and blood vessels

Symptoms :Symptoms :

PolyuriaPolydipsiaWeight lossSometimes polyphagiaBlurred vision

PolyuriaPolydipsiaWeight lossSometimes polyphagiaBlurred vision

DiagnosisDiagnosis

Symptoms of diabetes plus glucose > 200 mg/dl

or

Fasting plasma glucose > 126 mg/dl

or

2-h plasma glucose > 200 mg/dl during an OGTT

Symptoms of diabetes plus glucose > 200 mg/dl

or

Fasting plasma glucose > 126 mg/dl

or

2-h plasma glucose > 200 mg/dl during an OGTT

Keluhan Klinis Diabetes

Keluhan klasik + Keluhan klasik -

GDP >126 <126 >126 110-<126 <110 mg/dl

GDS >200 <200 >200 110-200 mg/dl

ulang GDS atau GDP

>126 <126 TTGO 2 jam

>200 <200

>>200 200 140-200 <140140-200 <140

DIABETES MELLITUS TGT GDPT NORMAL

Keluhan Klinis Diabetes

Keluhan klasik + Keluhan klasik -

GDP >126 <126 >126 110-<126 <110 mg/dl

GDS >200 <200 >200 110-200 mg/dl

ulang GDS atau GDP

>126 <126 TTGO 2 jam

>200 <200

>>200 200 140-200 <140140-200 <140

DIABETES MELLITUS TGT GDPT NORMAL

III. Klasifikasi Etiologis DMIII. Klasifikasi Etiologis DM

1. Diabetes Tipe-1 (destruksi sel beta)

AutoimunIdiopatik

2. Diabetes Tipe-2 ( resistensi insulin disertai defek sekresi insulin atau sebaliknya)

3. Diabetes Tipe lainA. Defek genetik fungsi sel beta MODY 1,2,3. DNA

mitokondriaB. Defek genetik kerja insulinC. Penyakit eksokrin pankreas; Pankreatitis, tumor pankreas,

pankreatektomi, pankreopati

fibrokalkulus

1. Diabetes Tipe-1 (destruksi sel beta)

AutoimunIdiopatik

2. Diabetes Tipe-2 ( resistensi insulin disertai defek sekresi insulin atau sebaliknya)

3. Diabetes Tipe lainA. Defek genetik fungsi sel beta MODY 1,2,3. DNA

mitokondriaB. Defek genetik kerja insulinC. Penyakit eksokrin pankreas; Pankreatitis, tumor pankreas,

pankreatektomi, pankreopati

fibrokalkulus

D. Endokrinopati

Acromegali, sindroma Cushing, Feokromositoma, hipertiroidisme

E. Karena obat/zat kimia

Vacor, pentamidin, asam nikotinat, Glukokortikoid, hormontiroid, tiazid, Dilantin, interferon alfa

F. Infeksi : rubellakongenital, CMV

G. Sebab imunologi yang jarang :

Antibodi anti insulin

H. Sindroma genetik lain:

Sindroma Down, Klinefelter, Turner dll.

4. Diabetes Gestasional

D. Endokrinopati

Acromegali, sindroma Cushing, Feokromositoma, hipertiroidisme

E. Karena obat/zat kimia

Vacor, pentamidin, asam nikotinat, Glukokortikoid, hormontiroid, tiazid, Dilantin, interferon alfa

F. Infeksi : rubellakongenital, CMV

G. Sebab imunologi yang jarang :

Antibodi anti insulin

H. Sindroma genetik lain:

Sindroma Down, Klinefelter, Turner dll.

4. Diabetes Gestasional

Type 1 Diabetes Type 1 Diabetes

Absolute insulin deficiencyidentified by :

• Serological evidence of autoimmune process

in the pancreatic islet • Genetic markers

Absolute insulin deficiencyidentified by :

• Serological evidence of autoimmune process

in the pancreatic islet • Genetic markers

Combination of :

• Insulin resistance and • Inadequate compensatory

insulin secretory response

Combination of :

• Insulin resistance and • Inadequate compensatory

insulin secretory response

Type 2 Diabetes Type 2 Diabetes

LIVER

ADIPOSE TISSUEADIPOSE TISSUE

PancreasPancreas

Insulin supply or action

GLUCOSEGLUCOSE

-

GLYCOGENOLYSISGLYCOGENOLYSIS

HGPHGP +G L UC O S E

G LYCOGEN

GLUCONEO

GENESIS

GLUCONEO

GENESIS

The Pathophysiology of Type 2 DMThe Pathophysiology of Type 2 DM

LIPOLYSISLIPOLYSIS

FFA FFA

+

Lactic AcidLactic Acid

Glycemic ControlGlycemic Control

HbA1c HbA1c cross-sectional, median valuescross-sectional, median values

0066

77

88

99

00 33 66 99 1212 1515

Hb

AH

bA 1

c1c (%

) (

%)

Years from randomisationYears from randomisation

ConventionalConventional

IntensiveIntensive

6.2% upper limit of normal range6.2% upper limit of normal range

}}0.9%0.9%

UKPDS Group Lancet 1998;352:837-53

UKPDS

16 % myocardial infarction p = 0.05216 % myocardial infarction p = 0.052

24 % for cataract extraction p = 0.046

Glycemic ControlGlycemic Control

12% any diab.-related endpoints p=0.030

25% microvascular endpoints p=0.010

21 % for retinopathy at 12 yrs p=0.015

33% for albuminuria at 12 yrs p=0.000054

UKPDS

An intensive glucose control policy of HbA1c

7.0 % vs 7.9 % reduces the risk of:

An intensive glucose control policy of HbA1c

7.0 % vs 7.9 % reduces the risk of:

Incidence of MCI and Microvascular Complications by Incidence of MCI and Microvascular Complications by Category of Updated Mean HbA1c (UKPDS Population)Category of Updated Mean HbA1c (UKPDS Population)Incidence of MCI and Microvascular Complications by Incidence of MCI and Microvascular Complications by Category of Updated Mean HbA1c (UKPDS Population)Category of Updated Mean HbA1c (UKPDS Population)

MCI

Microvascular endpoints

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

5 6 7 8 9 105 6 7 8 9 10Updated mean HbA1cUpdated mean HbA1c

ConclusionConclusion• The UKPDS has shown that intensive blood glucose

control reduces the risk of diabetic complications, the greatest effect being on microvascular complications (and less on macrovascular com-lications)

• Observational Study using the updated mean HbA1c in the UKPDS population reveales that the rate of increase of risk for microvascular disease with hyperglycemia is greater than that for macrovascular disease

• The lower the glycemia the lower the risk of complications

• The UKPDS has shown that intensive blood glucose control reduces the risk of diabetic complications, the greatest effect being on microvascular complications (and less on macrovascular com-lications)

• Observational Study using the updated mean HbA1c in the UKPDS population reveales that the rate of increase of risk for microvascular disease with hyperglycemia is greater than that for macrovascular disease

• The lower the glycemia the lower the risk of complications

Longer term : Prevent complications

Reduce morbidity and mortality

Longer term : Prevent complications

Reduce morbidity and mortality

ManagementManagement

Short term :Eliminate symptoms

Maintain general well being

Short term :Eliminate symptoms

Maintain general well being

Strategy :Normalizing glucose,

lipid, and insulin levels

Strategy :Normalizing glucose,

lipid, and insulin levels

Activities :Management with holistic

approach and self care principles

Activities :Management with holistic

approach and self care principles

A. Aim A. Aim

Treatment ModalitiesTreatment Modalities

• Diet/Medical nutrition therapy• Exercise• Anti hyperglycemic agents• Education• Pancreas transplantation• Cloning treatment (experiment)

• Diet/Medical nutrition therapy• Exercise• Anti hyperglycemic agents• Education• Pancreas transplantation• Cloning treatment (experiment)

Nutrient Composition of Diabetic Diet

PERKENI A D A and B D A(Indonesian Soc.of Endoc.)

Nutrient Composition of Diabetic Diet

PERKENI A D A and B D A(Indonesian Soc.of Endoc.)

Carbohydrate Fat Protein

20-25%10-15%

60-70%

Diet/Nutrition Therapy/Meal planningDiet/Nutrition Therapy/Meal planning

Carbohydrate Fat Protein

30%10-15%

55%

Exercise

30 minutes: 3 - 4 times / week

ContinuousRhytmicalIntervalProgressiveEndurance training

Exercise

30 minutes: 3 - 4 times / week

ContinuousRhytmicalIntervalProgressiveEndurance training

Anti Diabetic Agents

Hypoglycemic Agents

Anti Hyperglycemic Agents

Anti Diabetic Agents

Hypoglycemic Agents

Anti Hyperglycemic Agents

Adipose tissueAdipose tissue

Sites of Action of Antihyperglycemic AgentsSites of Action of Antihyperglycemic AgentsPancreasPancreas

1. Insulin 1. Insulin

GLUCOSEGLUCOSE

GLUCONEOGENESIS

GLUCONEOGENESIS

HGPHGP-

NN

IntestineIntestine

2. Insulin secretagogue

2. Insulin secretagogue

4. Acarbose4. Acarbose

3. MetforminTZD

3. MetforminTZD

3. MetforminTZD

3. MetforminTZD

+

GLYCOGENOLYSISGLYCOGENOLYSIS

+

-

+

+

1a. Insulin 1a. Insulin

Insulin actions include :Insulin actions include :

• Ability of insulin to lower circulating glucose concentrations

Suppress glucose production : liver Stimulate glucose utilization : muscle plus fat

• Additional metabolic, vascular & mitogenic actions

• Ability of insulin to lower circulating glucose concentrations

Suppress glucose production : liver Stimulate glucose utilization : muscle plus fat

• Additional metabolic, vascular & mitogenic actions

LIVER

ADIPOSE TISSUE

The Suppression Hepatic Glucose ProductionThe Suppression Hepatic Glucose ProductionPancreas

Insulin

GLUCOSEGLUCOSE

GLUCONEOGENESIS

HGP

GLYCOGENOLYSIS

-

NN

LIVER

ADIPOSE TISSUE

The Stimulation of Glucose UptakeThe Stimulation of Glucose UptakePancreas

Insulin

GLUCOSEGLUCOSE

GLUCONEOGENESIS

HGP-

GLYCOGENOLYSIS

G LYCOGEN

NN G L UC O S E

+

Glucose Uptake

Glucose Uptake

LIVER

ADIPOSE TISSUEADIPOSE TISSUE

The Stimulation of Lipogenesis in Adipose TissueThe Stimulation of Lipogenesis in Adipose TissuePancreas

Insulin

GLUCOSEGLUCOSE

GLUCONEOGENESIS

HGP-

GLYCOGENOLYSIS

G LYCOGEN

G L UC O S E

+

Glucose Uptake

Glucose Uptake

LipogenesisLipogenesis+

NN

FFA

Alternative Routes for Insulin DeliveryRoute Advantage Disadvantage

Alternative Routes for Insulin DeliveryRoute Advantage Disadvantage

IntraperitonealIntraperitoneal

IntravenousIntravenous

NasalNasal

Pump equiredCatheter blockage Infection riskRisk of large insulin

reservoir

Pump requiredCatheter blockage PhlebitisHyperinsulinemia

Nasal irritationLow bioavailabilityInterference by resp.

infection

Pump equiredCatheter blockage Infection riskRisk of large insulin

reservoir

Pump requiredCatheter blockage PhlebitisHyperinsulinemia

Nasal irritationLow bioavailabilityInterference by resp.

infection

Portal absorptionGood bioavailabilityPhysiologic profiles

Portal absorptionGood bioavailabilityPhysiologic profiles

Good bioavailabilityPhysiologic ProfilesGood bioavailabilityPhysiologic Profiles

Physiologic profilesEasy useNo device required

Physiologic profilesEasy useNo device required

Alternative Routes for Insulin Delivery(cont.)

Alternative Routes for Insulin Delivery(cont.)

Low bioavailability

Variable absorption

Low bioavailability

Variable absorption

Low bioavailability

Variable absorption

Low bioavailability

Variable absorption

PulmonaryPulmonary

OralOral

Physiologic profilesSimple deviceEasy use

Physiologic profilesSimple deviceEasy use

Easy useAcceptableEasy useAcceptable

Route Advantage DisadvantageRoute Advantage Disadvantage

Implantable PumpsImplantable PumpsMiniMed Implantable Pump (MIP) Model

2000Infusaid Model 100

Artificial and Bio-artificial Pancreas System

Islet TransplantationFetal and Neonatal Pancreas

Transplantation

MiniMed Implantable Pump (MIP) Model 2000

Infusaid Model 100

Artificial and Bio-artificial Pancreas System

Islet TransplantationFetal and Neonatal Pancreas

Transplantation

Alternative Routes for Insulin Delivery(cont.)

Alternative Routes for Insulin Delivery(cont.)

Indications of Insulin Treatment

Indication for the use of insulin in Type 2 DM

• In severe metabolic decompensation• Ketoacidosis• Hyperosmolar non ketotic coma • Lactic acidosis • Severe stress :

Systemic infectionMajor surgery

• Weight loss within a short period of time• Pregnancy if diet does not succeed to control

glycemia• OHA failure or contra-indication of OHA

Indications of Insulin Treatment

Indication for the use of insulin in Type 2 DM

• In severe metabolic decompensation• Ketoacidosis• Hyperosmolar non ketotic coma • Lactic acidosis • Severe stress :

Systemic infectionMajor surgery

• Weight loss within a short period of time• Pregnancy if diet does not succeed to control

glycemia• OHA failure or contra-indication of OHA

The Pharmacology of InsulinThe Pharmacology of Insulin

Lispro AspartRegularNPH

LenteUltra lenteGlargine

Lispro AspartRegularNPH

LenteUltra lenteGlargine

0.10-0.250.10-1.01.0-3.0

1.5-4.02-62-4

0.10-0.250.10-1.01.0-3.0

1.5-4.02-62-4

0.75-2.01.0-4.05.0-7.0

4.0-8.08.0-12None

0.75-2.01.0-4.05.0-7.0

4.0-8.08.0-12None

4.0-5.04.0-1013-18

13-2018-30

-24

4.0-5.04.0-1013-18

13-2018-30

-24

Yes w RI+/- w lispro

+/-+/-

NO !!!precipitate

Yes w RI+/- w lispro

+/-+/-

NO !!!precipitate

MinimalModerate

High

HighVery High

Moderate tohigh

MinimalModerate

High

HighVery High

Moderate tohigh

Onset(h)

Onset(h)

Peak(h)

Peak(h)

Duration (h)

Duration (h)

Miscibility withLispro or

Reg. insulin

Miscibility withLispro or

Reg. insulin

Variability inabsorption

Variability inabsorption

Pre-mixed (70/30,50/50,lispro mix 75/25) equivalent to sum of above componentsPre-mixed (70/30,50/50,lispro mix 75/25) equivalent to sum of above components

Buse BB Diabetes Spectrum 2000

Insulin available in IndonesiaInsulin available in Indonesia

Short acting insulin Long acting insulin

Actrapid Human U 40, U100 PZI U40 Humulin R U40, U100 Ultratard U100 Regular Insulin U40

Intermediate acting insulin Penfil

Monotard U40, U100 Actrapid penfil Insulatard U40, U100 Insulatard penfil Humulin N U40, U100 Mixtard 30/40 penfil NPH U40 Humulin R penfil

Humulin 30/70 penfil

Short acting insulin Long acting insulin

Actrapid Human U 40, U100 PZI U40 Humulin R U40, U100 Ultratard U100 Regular Insulin U40

Intermediate acting insulin Penfil

Monotard U40, U100 Actrapid penfil Insulatard U40, U100 Insulatard penfil Humulin N U40, U100 Mixtard 30/40 penfil NPH U40 Humulin R penfil

Humulin 30/70 penfil

1 b. Insulin Analogues1 b. Insulin Analogues

• Genetic engineering • Main aim : Solubility reduction • Substitution/addition of amino acid residue of

insulinShort acting :

Lispro: B28-lysine, B29-proline

X14 : B28-aspartateLong acting:

B31-B32 arginine, A21-glycine

• Immunogenicity

• Genetic engineering • Main aim : Solubility reduction • Substitution/addition of amino acid residue of

insulinShort acting :

Lispro: B28-lysine, B29-proline

X14 : B28-aspartateLong acting:

B31-B32 arginine, A21-glycine

• Immunogenicity

2. Insulin Secretagogues2. Insulin Secretagogues

• Induce insulin secretion

• Potentiate nutrient-induced insulin secretion

• Antagonize inhibitors of insulin secretion

• Calcium, Cyclic AMP and Adrenoreceptor Manipulator

• Other Insulin secretagogues

• Induce insulin secretion

• Potentiate nutrient-induced insulin secretion

• Antagonize inhibitors of insulin secretion

• Calcium, Cyclic AMP and Adrenoreceptor Manipulator

• Other Insulin secretagogues

Insulin Secretagogues (cont.)Insulin Secretagogues (cont.)

ATP-sensitive Potassium Channel Inhibitors

Long acting :Sulphonylureas

Short acting :Repaglinide : Benzoic acid derivative

Nateglinide : Phenyl alanine derivative

ATP-sensitive Potassium Channel Inhibitors

Long acting :Sulphonylureas

Short acting :Repaglinide : Benzoic acid derivative

Nateglinide : Phenyl alanine derivative

SulphonylureasSulphonylureas

• Have been a mainstay of type 2 diabetes treatment for > 40 years

• Bind to an SU receptor (SUR) on the-cell which leads to depolarisation of -cell membrane and stimulates insulin secretion

• First generation : chlorpropamide• Second generation : glibenclamide, glipizide,

gliclazide• Third generation : glimepiride• Attention : Hypoglycemia (less in glipizide GITS and

glimepiride)

• Have been a mainstay of type 2 diabetes treatment for > 40 years

• Bind to an SU receptor (SUR) on the-cell which leads to depolarisation of -cell membrane and stimulates insulin secretion

• First generation : chlorpropamide• Second generation : glibenclamide, glipizide,

gliclazide• Third generation : glimepiride• Attention : Hypoglycemia (less in glipizide GITS and

glimepiride)

Depola-risation

Ca 2+ Voltage DependentCa 2+Channel (VDCC)

ProinsulinProinsulin

ClosedClosed

ATP SensitiveK+ Channel

SS 01

Islet cellIslet cell

OpenOpen

Ca 2+Ca 2+

INSULIN INSULIN

C-PEPTIDE

SU

SUR

ATPADPATPADPATPADPATPADP

Glucose

Am. acid

GlucokinaseGlucokinase

Metabolism Metabolism

Mode of Action of Sulphonylureas

3. Insulin Sensitizers (1)3. Insulin Sensitizers (1)

Metformin

– Anti hyperglycemic not hypoglycemic– Do not target -cell– Suppress HGP (hepatic glucose production)– Enhance tissue sensitivity to insulin to promote

uptake of glucose into muscle– Cardioprotective effect on obese

patients(UKPDS)– Often used in combination with Sus– Little effect on post prandial hyperglycemia– Gastrointestinal discomfort

Metformin

– Anti hyperglycemic not hypoglycemic– Do not target -cell– Suppress HGP (hepatic glucose production)– Enhance tissue sensitivity to insulin to promote

uptake of glucose into muscle– Cardioprotective effect on obese

patients(UKPDS)– Often used in combination with Sus– Little effect on post prandial hyperglycemia– Gastrointestinal discomfort

Thiazolidinediones

– Anti hyperglycemic not hypoglycemic– Increase expression of transmembrane glucose

transporters (GLUT 1 and GLUT 4)– Increase insulin-stimulated glucose disposal– Increase insulin-stimulated glucose uptake and

metabolism by muscle and fat– Suppression of hepatic glucose production– Reduce plasma triglycerides

PioglitazoneRosiglitazone

Thiazolidinediones

– Anti hyperglycemic not hypoglycemic– Increase expression of transmembrane glucose

transporters (GLUT 1 and GLUT 4)– Increase insulin-stimulated glucose disposal– Increase insulin-stimulated glucose uptake and

metabolism by muscle and fat– Suppression of hepatic glucose production– Reduce plasma triglycerides

PioglitazoneRosiglitazone

Insulin SensitizersInsulin Sensitizers (2)

4. Inhibition of CHO digestion and absorption

4. Inhibition of CHO digestion and absorption

• Alpha glucosidase inhibitors

acarbose

• Plant fibre supplements

guar gum

bran

• Alpha glucosidase inhibitors

acarbose

• Plant fibre supplements

guar gum

bran

• Ingested with meals

• Delay the digestion of complex carbohydrate

• Competitive inhibition of alpha glucosidase in the intestine

• Blunting postprandial glucose spikes

• Gastrointestinal side effects

• Ingested with meals

• Delay the digestion of complex carbohydrate

• Competitive inhibition of alpha glucosidase in the intestine

• Blunting postprandial glucose spikes

• Gastrointestinal side effects

Alpha Glucosidase Inhibitors (Acarbose)

Alpha Glucosidase Inhibitors (Acarbose)

Oral Anti Hyperglycemic Agents that Have Potential Effect of Overcoming “Peaks and Valleys”

Oral Anti Hyperglycemic Agents that Have Potential Effect of Overcoming “Peaks and Valleys”

Dietetic

Reduced carbohydrate intake

Spreading carbohydrate intake

Carbohydrate according to 24 hr blood glucose profile

Dietary fibres

Low glycemic index food

Dietetic

Reduced carbohydrate intake

Spreading carbohydrate intake

Carbohydrate according to 24 hr blood glucose profile

Dietary fibres

Low glycemic index food

PharmacologicalPharmacologicalSpecific

Acarbose

Repaglinide

Nateglinide

Insulin lispro

Nasal/pulmonary insulin

Glucagon-like peptide-1

Amylin analogues

Specific

Acarbose

Repaglinide

Nateglinide

Insulin lispro

Nasal/pulmonary insulin

Glucagon-like peptide-1

Amylin analogues

Non-specific

Sulphonylurea

glipizide GITS glimepiride

Metformin

Thiazolidinediones

Long acting insulin

Non-specific

Sulphonylurea

glipizide GITS glimepiride

Metformin

Thiazolidinediones

Long acting insulin

Combination Therapy in T2DM:Insulin Plus Oral Hypoglycemic Agents

Insulin Plus Sulphonylurea - BIDS Some insulin is endogenous, with natural

secretory patternBiguanide Plus Insulin

Reduces hepatic insulin resistanceMay achieve better control with less insulinCan reduce weight gain

Alpha Glucosidase Inhibitor Plus InsulinReduces posotprandial glucose level

Thiazolidinedione Plus InsulinReduces peripheral insulin resistanceReduces insulin requirementMust balance TZD and insulin carefully to minimize

weight gain

Benefits of Insulin and Oral Agents CombinationBenefits of Insulin and Oral Agents Combination

• Improves glycemic controlTreats multiple physiologic abnormalities

• Less insulin is needed to achieve good glycemic control

• Reduces potensial for weight gain

• Patients: • more practical and less frightening• improved psychological acceptance, patients continue the oral drugs

• less / minimal education is needed• treatment can be started in an • outpatients-setting • better compliance, and cost may be less

• Improves glycemic controlTreats multiple physiologic abnormalities

• Less insulin is needed to achieve good glycemic control

• Reduces potensial for weight gain

• Patients: • more practical and less frightening• improved psychological acceptance, patients continue the oral drugs

• less / minimal education is needed• treatment can be started in an • outpatients-setting • better compliance, and cost may be less

Oral Hypoglycemic Drugs Available in Indonesia Initial dose Maximal dose Frequency of

mg/day mg/day administration /day

SulphonylureaGlibenclamide 2,5 15-20 1-2 XGliclazide 80 240 1-2 XGlipizide : 5 20 2-3 XGlipizide GITS 5 20 1-2 XGliquidone 30 120 1 XChlorpropamide 50 500 1 XGlimepiride 0,5 6 1 X

MeglitinideRepaglinide 1.5 mg 8 mg 3XNateglinide 120 mg 360 mg 3X

Metformin 500 3000 1-3 X

Alpha glucosidase inhibitor Acarbose 50 300 3 X

Oral Hypoglycemic Drugs Available in Indonesia Initial dose Maximal dose Frequency of

mg/day mg/day administration /day

SulphonylureaGlibenclamide 2,5 15-20 1-2 XGliclazide 80 240 1-2 XGlipizide : 5 20 2-3 XGlipizide GITS 5 20 1-2 XGliquidone 30 120 1 XChlorpropamide 50 500 1 XGlimepiride 0,5 6 1 X

MeglitinideRepaglinide 1.5 mg 8 mg 3XNateglinide 120 mg 360 mg 3X

Metformin 500 3000 1-3 X

Alpha glucosidase inhibitor Acarbose 50 300 3 X

ADA Treatment Goals for Glycemic Control

Glycemia Normal Goal Further Action

Required*

Average Preprandial <110 80 to 120 <80Fasting Glucose (mg/dL) >140

Average Postprandial <140 <160 >180Glucose (mg/dL)

HbA1C (%) <6 <7 >8

Further Action Required = Get off your rear and DO something

Adapted from the Expert Committee on the Diagnosis and Classification of Diabetes MellitusDiabetes Care 1999;22:S32-S41

Proposed New Treatment Paradigm for Type 2 Diabetes

Medical Nutrition Therapy, Exercise , Education and SMBG

HbA1c < 7 % HbA1c 7- 8 % HbA1c > 8 %HbA1c > 8 %

Consider oralmonotherapy

Add insulin sensitizer or secretagoque

Add insulin sensitizer or secretagoque

Add insulin sensitizer and secretagoque

Add insulin sensitizer and secretagoque

Target not MetTarget not Met Target not MetTarget not Met Target not MetTarget not Met

Start Insulin or add Third oral agent

Full Insulin therapy With Or without Oral agent(s)

Full Insulin therapy With Or without Oral agent(s)

Complications :Complications :

KetoacidosisNonketotic

Hyperosmolar syndrome

KetoacidosisNonketotic

Hyperosmolar syndrome

RetinopathyNephropathyNeuropathy

RetinopathyNephropathyNeuropathy

MacroangiopathyMacroangiopathy

Chronic :Chronic :Acute :Acute :

MicroangiopathyMicroangiopathy

CADPVD

Stroke

CADPVD

Stroke

Treatment Priorityof Type 2 DM

Treatment Priorityof Type 2 DM

Glucose control as near to normal as

reasonably possible

Glucose control as near to normal as

reasonably possible

Microvascular

disease

Microvascular

disease

Control of Insulin resistance: Hyperinsulinemia, Obesity,

Glucose intolerance, Dyslipidemia, Hypertension,

Procoagulant state

Control of Insulin resistance: Hyperinsulinemia, Obesity,

Glucose intolerance, Dyslipidemia, Hypertension,

Procoagulant state

Macrovascular disease

Macrovascular disease

Insulin resistance

Insulin resistance

PAI-1,Factor VII, FibrinogenPAI-1,Factor VII, Fibrinogen

HyperglycemiaHyperglycemia

HypertensionHypertension

Pro-coagulant StatePro-coagulant State

ObesityObesity

DyslipidemiaDyslipidemia

Cardiovasculardisease

Cardiovasculardisease

Intervention/Control

Control of Insulin ResistanceControl of Insulin Resistance