inspire papdi modul cd 1

INTRODUCTION

Sponsored by PT. Novo Nordisk Indonesia

New INSPIRE by PERKENI and STENO Diabetes Center A N ti l Di b t M t CA National Diabetes Management Course

Overall Training Objectivesg j

To provide participants with a holistic understanding of To provide participants with a holistic understanding of To provide participants with a holistic understanding of diabetes management – from diagnosis to late-stage complications

To provide participants with a holistic understanding of diabetes management – from diagnosis to late-stage complications

To provide participants with practical tools, guidelines, demonstrations and take-home educational materials to improve and optimize their diabetes treatment

To provide participants with practical tools, guidelines, demonstrations and take-home educational materials to improve and optimize their diabetes treatment

To emphasize and demonstrate the importance of early To emphasize and demonstrate the importance of early p p ytreatment of diabetes to avoid long-term complications

p p ytreatment of diabetes to avoid long-term complications

About INSPIRE Training in IndonesiaAbout INSPIRE Training in Indonesia

Curriculum Sponsorship

• Curriculum, workshops and cases designed in

• The INSPIRE Training courses, the development of

collaboration between PB. PERKENI and STENO Diabetes

the curriculum and all support programs are

Coordination and

liSTENO Diabetes Center

• Joint PERKENI –STENO certificates

sponsored by PT. Novo Nordisk Indonesia to support and

Alignment

STENO certificateswill be distributed for a participation rate of 90%

support and enhance the quality of diabetes training across Indonesia

Why INSPIRE?Why INSPIRE?

BE INSPIRED AS A DOCTOR

…TO INSPIRE YOUR PATIENTSDOCTOR… PATIENTS

A TRULY UNIQUE PLACEA TRULY UNIQUE PLACE• An independent research and patient care institution funded by the

capital Region of Copenhagen and Novo Nordisk

P ti t h d d ti f i l i l• Patient care, research and education – focusing exclusively on diabetes care and prevention

• One of the leading diabetes research and health promotion centers in the worldthe world

• Treating 6.200 patients with Type 1 and Type 2 Diabetes through the ‘team-based’ method

STENO EDUCATION CENTERFacts:Facts:

• Collaborating with Novo Nordisk and the Capital Region on education of HCPs• Frontiers Steno Symposium• STAR courses in India/Middle East/China• Educational tools• Partnerships with endocrine society's in selected countries (China / Indonesia)

Rules of the INSPIRE ProgramRules of the INSPIRE Program

RULES

• Certificates can only be i f i i 80%

RULES

given for minimum 80% attendance

Li it M bil Ph A ti it• Limit Mobile Phone Activity to the Coffee Breaks

B b k i f• Be back on time after lunch- and coffee breaks

Why do we see a massive increase in people with Type 2 Diabetes across the World?

Aging population UrbanisationUnhealthy lifestyle choices

Dietary changes Reduced physical activity

Cockram CS 2000. HKMJ; 6 (1): 43-52Mohan et al 2007. Indian J Med Res; 125: 217-230

Adapted from IDF Diabetes Atlas 4th ed., 2009

High Blood Glucose is now the 3rd biggest risk factor contributor to cardio-vascular deathsfactor contributor to cardio vascular deaths globally

Alcohol use

Childhood underweight

Indoor smoke from solid fuels

Overweight and Obesity

High Cholesterol

Unsafe Sex

Tobacco

High Blood Glucose

Physical Inactivity

0 1,000 2,000 3,000 4,000 5,000 6,000 7,000 8,000

Raised Blood Pressure

Tobacco

Attributable deaths due to selected risk factors (000’)

Source: WHO 2011. Global Atlas on CVD prevention and Control 1-164

Diabetes is developing much faster than ti i t d i I d ianticipated in Indonesia…

RISKESDAS Survey 2007

Diagnosed people with Diabetes

Undiagnosed people with Diabetes

Total people with diabetes

Total people with IGT**

1.5% 4.2% 5.7% 10.2%

Approximately 10 million people with diabetes in Indonesia

* Source: RISKESDAS Survey 2007 – 24.417 subjects , >15 years ol from 33 provinces ** IFT = Impaired Glucose Tolerance

…and our diabetes patients are not in good glycemic controlDiabCare Indonesia 2008 illustrated the need for more intensiveDiabCare Indonesia 2008 illustrated the need for more intensive treatment to decrease FPG and PPG

n: 1.823 patients with diabetesmg/dl

208

160

180

200

220

evel

144

100

140

100

120

140

160

c Contr

ol L

40

60

80

100

Gly

cem

i

0

20

PPG (mg/dl)FPG (mg/dl)

PERKENI GuidelinesDiabCare 2008

Source: Novo Nordisk Data on File

P T t 20 i tPre-Test – 20 minutesPre-Test

LECTURE

Early Detection and Standardized Diabetes

Monitoring

Early Detection and Standardized Diabetes Lecture:

yMonitoring

30 minutes

Early Detection and Standardized Diabetes MonitoringMonitoringLecture

Main Learning PointsMain Learning Points

• Understand the importance of treating diabetes p gand reaching individual targets to avoid complications

• Understand the process from screening to diagnosis and the associated national guidelines

• Understand the reason and need for routine follow-up and intensify treatment on diabetes via blood glucose- and HbA1c monitoringblood glucose and HbA1c monitoring

Some Definitions before we start…

Common Definitions

Abb i ti D fi itiAbbreviation Definition

NGT Normal Glucose Tolerance (Gula Darah Normal)

FPG Fasting Plasma Glucose (Gula Darah Puasa)

PPG Post-Prandial Plasma Glucose (Gula Darah Post Prandial)

IGT Impaired Glucose Tolerance(Toleransi Glukosa Terganggu)

IFT Impaired Fasting Glucose IFT (Gula Darah Puasa Terganggu)

HbA1c Average amount of glucose in the bloodstreams over a 3-month period

Classification of Diabetes

• Type 1 diabetes

• Absolute insulin deficiency due to the destruction of• Absolute insulin deficiency due to the destruction of pancreatic beta-cells

• Type 2 diabetes

• Type 2 is characterized by insulin resistance with relative insulin deficiency to a predominately secretary defect with insulin resistance

• Other specific types

• Gestational diabetes

• Glucose intolerance first detected in pregnancy that often resolves after the birth of the baby

Diabetes Care 1997; 20: 1183-1197

Difference between Type 1 and Type 2 Diabetes

Comparison of Type 1 and Type 2 Diabetes

Features Type 1 Diabetes Type 2 DiabetesFeatures Type 1 Diabetes Type 2 Diabetes

Onset Sudden Gradual

Age at Onset Any age (mostly young) Mostly in adultsAge at Onset Any age (mostly young) Mostly in adults

Body Habitus Thin or normal Often obese

K t id i C RKetoacidosis Common Rare

Autoantibodies Usually present Absent

E d L b N l d dEndogenous Insulin

Low or absent Normal, decreased or increased

Prevalence Less prevalent More prevalent, typically 90-95% of all people with90 95% of all people with diabetes

Type 2 diabetes is a progressive disease

Lebovitz. Diabetes Reviews 1999;7:139–53 (data are from the UKPDS population: UKPDS 16. Diabetes 1995;44:1249–58)

HOMA: homeostasis model assessment

Diabetes – elevated blood glucose due to insufficient insulin secretioninsufficient insulin secretion

Normal glucose and insulin excursions

Early Type 2 Diabetes Glucose and insulin excursions

400 120

Glucose Insulin

400 120

Glucose Insulin

200

300

60

80

100

e m

g/

dL In

sulin

U 200

300

60

80

100

e m

g/

dL In

sulin

10020

40

Glu

cos

U/

mL 100

20

40

Glu

cose

U/

mL

06:00 10:00 18:0014:00 02:0022:00 06:00

Time of Day

Bre

akfa

st

Lu

nch

Din

ner

06:00 10:00 18:0014:00 02:0022:00 06:00

Time of Day

Bre

akfa

st

Lu

nch

Din

ner

t t

Classical Diabetes Symptoms

Polyuria • Excessive Urination at night

Polyphagia • Excessive HungerPolyphagia • Excessive Hunger

Polydipsia • Excessive Thirst

Unexplained weight loss

• Weight Loss even if food in-take is normal

Other Diabetes Symptoms

Blurred Vision • Damaging blood vessels in the eyes

Numbness and/or Tingling

the eyes

• Numbness and tingling in hands, legs and feet

Fatigue

legs and feet

• Frequent fatigue regardless of e e cise

Itchy Skin

of exercise

• affects legs, feet, and hands

Impotence

g , ,

• Physical and Physiologicalp ys ca a d ys o og ca

4 Simple Steps from Screening to Diagnosis

Conduct 1st Blood Test2

Conduct 2nd Blood Test (if required) and establish Diagnosis

3Screen patients with diabetes risk factors

1

Inform Patient and Initiate treatment

4

Initiate treatment

Step 1: Risk Factors – PERKENI screening risk factor guidelinefactor guideline

Unmodifiable Risk Modifiable Risk Diabetes Associated RiskRisk

• Race and Ethnic

Family History of

• Overweight (BMI >23)

Hypertension >

• Polycystic Ovary

Syndrome (PCOS) or• Family History of

Diabetes

• History of Gestational

Diabetes

• Hypertension >

140/90 mmHg

• Dyslipidemia (HDL <

35 mg/dl and/or

Syndrome (PCOS) or

another clinical

condition related to

insulin resistanceDiabetes

• History of delivery a

baby more than

4 000g

35 mg/dl and/or

triglycerides >250

mg/dl

• Unhealthy Diet

insulin resistance

• Metabolic Syndrome

(IGT, IFG, History of

Coronary Artery4.000g

• History of low birth

weight <2.500g

• Unhealthy Diet

• Limited Physical

Activity

Coronary Artery

Disease , stroke

and/or PAD)

Source: KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2

Step 2: Conduct 1st Blood Test

Clinical Test

(+) Classic Symptoms

(-) Classical Symptoms

FBG

RBG

>126

>200

<126

<200

FBG

RBG

>126

>200

<100

<140

100-125

140-199

Repeat FBG or RBG

2 Hour Post loading Plasma Glucose

Diabetes Mellitus IGT IFG Normal


Step 3: Conduct 2nd Blood Test (if required) and Establish Diagnosisand Establish Diagnosis

Clinical Test

(+) Classic Symptoms

(-) Classical Symptoms

FBG

RBG

>126

>200

<126

<200

FBG

RBG

>126

>200

<100

<140

100-125

140-199

Repeat FBG or RBG

2 Hour Post loading Plasma Glucose

>126

>200

<126

<200

PPG >200 140-199 <140

Diabetes Mellitus IGT IFG Normal


Step 4: Inform Patient and Initiate Treatment

Diabetes Mellitus IGT IFG

E l ti f N t iti l St t Ed ti• Evaluation of Nutritional Status

• Evaluation of Diabetes

Complications

• Education

• Food Regulation

• Physical Exercise

• Evaluation of Required Food

Regulation

• Decision on medines

• Ideal Body Weight

• OADs are unnecessary at

this stageg


Cut-points: Diabetes, IGT and IFG

md/dl

FP

G)

md/dl

Diabetes

Glu

cose

(F

126

IFG (Impaired Fasting Glucose

ng

Pla

sma

100

NGT (Normal Glucose

Fasting Glucose

IGT (Impaired Glucose

Tolerance)Diabetes

d/dl

Fast

in

140 200

Glucose Tolerance)

md/dl

2-hour Plasma Glucose (PPG)

140 200

Diagnosis of Type 2 DiabetesKONSENSUS: Pengelolaan Dan Pencegahan DM Type 2KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2

1. Symptoms of Diabetesy p

• Random plasma glucose concentration > 200 mg/dl

Or2. Fasting Plasma Glucose:

• FBG > 126 mg/dl. No calorie intake for at least 8 hours

N d b d i i i d d d• Need to be repeated twice in two independent days

3 2-hour post-OGTT

Or

3. 2-hour post-OGTT

• OGTT > 200 mg/dl. 75 g. of glucose dissolved in water

The Importance of treating Type 2 DiabetesType 2 diabetes is a progressive diseaseType 2 diabetes is a progressive disease

Diagnosis

Postprandial glucose

Diagnosis

Glucose Fasting glucose

Insulin Insulin resistance

Inadequateβ-cell function Insulin secretion

PrediabetesNGT Di b t

Macrovascular changes

Microvascular changes Insulin secretion

Adapted from Type 2 Diabetes BASICS. International Diabetes Center 2000

Prediabetes(IFG/IGT)NGT Diabetes

Treatment therapies for Type 2 diabetesWhen and How to start treatmentWhen and How to start treatment

START TREATMENT OAD TREATMENT START INSULIN INSULIN INTENSIFICATION

Lifestyle + +-other OAD or GLP-1

Basal

Basal Premix Basal + BolusMetformin or GLP 1

agonists Insulin Insulin Bolus Insulin

HbA1c ≥7.0%

Adapted from Raccah et al. Diabetes Metab Res Rev 2007;23:257.

What is good glycemic control?

• Overall aim to achieve glucose levels as close to normal as possiblepossible

• Minimise development and progression of microvascular and macrovascular complications

FPG <130 mg/dL

HbA1c< 7.0%

PPG<180 mg/dL

ADA1

FPG <110 mg/dl

HbA1c< 6.5%

PPG<145 mg/dL

IDF2

PERKENI3 FPG<100 mg/dl

HbA1c< 7%

PPG<140 mg/dl

1. American Diabetes Association Diabetes Care 2009;32 (Suppl 1):S1-S972. IDF Clinical Guidelines Task Force. International Diabetes Federation 2005. 3. PERKENI 2011 Konsensus .

Risk of Complications increases as Hb1Ac increases and that’s why diabetes must be treatedincreases and that s why diabetes must be treated

80

60 Microvascular disease

0 p

atie

nt-

20

40 Myocardial infarction

e per

1.0

00

year

s

05 6 7 8 9 10 11In

ciden

ce

Mean HbA1c (%)

Adjusted for age, sex, and ethnic group. The relationship between A1C and mg/dl is described

12697 154 183 212 240 269 Mean mg/dl

Stratton IM et al. BMJ 2000;321:405–12

j g , , g p p g/by the formula 28.7 X A1C – 46.7 = mg/dl.

The benefits of good blood glucose control are lclear

Good control isMyocardial infarctionGood control is

≤ 7.0% HbA1c

HbA1c measures

infarction

-14%1c

the average blood glucose level over the

Microvascular complicationsHbA1c

last three months -37%

b 1c

-1%

Deaths related to diabetes

Source: UKPDS = United Kingdom Prospective Diabetes Study. Stratton IM et al. BMJ. 2000;321(7258):405-412.

-21%

Practical Monitoring Scheme

Source: Konsensus Pengelolaan dan Pencegahan DMT2 di Indonesia. PERKENI. 2011. Diabetes Care 2012. Penatalaksanaan Diabetes Melitus Terpadu. 2009

Practical Monitoring Scheme Cont…

Source: Konsensus Pengelolaan dan Pencegahan DMT2 di Indonesia. PERKENI. 2011. Diabetes Care 2012. Penatalaksanaan Diabetes Melitus Terpadu. 2009

ABCD Strategy to guide Diabetes Treatmentgy g

ABCD Strategy

Age (older) • Increased risk for hypoglycemia & comorbidities• Less stringent therapy• Reduce the use of kidney-excreted drugs if possible

Body Weight • BW neutral (gliptins, acarbose, DPPIV inhibitors, long-acting insulin analogues),

• BW gain (human insulin, sulphonylureas, TZDs)• BW loss (metformin GLP1 analogues)• BW loss (metformin, GLP1 analogues)

Complications • Major macro- & microvascular complication less stringent

• Consider renal or heart failure• Consider renal or heart failure

Duration of Disease • Strict glycemic control at the early period of the disease better prevention of macro & microvascular complications

Source: Diabetes Metab Res Rev 2010; 26: 239–244

p

Individualized Treatment based on several criteria to control blood glucoseto control blood glucose

Inzucci SE, et al. Diabetologia. 2012

LECTURE

Diabetes and itsCo-morbidities-Hypertension

and Dyslipidemia

Diabetes and its Co-morbidities –Hypertension and Dyslipidemia

Lecture:

Hypertension and Dyslipidemia

Diabetes

HypertensionDyslipidemia

30 minutes

Diabetes and its Co-morbidities – Hypertension and Dyslipidemiaand DyslipidemiaLecture

Main Lea ning PointsMain Lea ning PointsMain Learning PointsMain Learning Points

• Understand the relationship between diabetes and hypertensionhypertension

• Understand how hypertension should be treated and how hypertension patients should be treated

• Understand the relationship between diabetes and dyslipidemia

• Understand how dyslipidemia should be treated and how dyslipidemia patients should be treated

Why focus on the triangle of diabetes, hypertension and dyslipidemia?hypertension and dyslipidemia?

“Triangular Focus’ Treatment Implicationsg p

• 40-60% of type 2 diabetes patients will also have either

Diabetes

patients will also have either hypertension, dyslipidemia or both

• Hypertension and Dyslipidemia

Hypertension

Dyslipidemia

yp y pare both well established risk factors for diabetes-related complications like CVD and nephropathy

• Early and correct treatment of hypertension and dyslipidemia can delay the on-set of diabetes complicationscomplications

Diabetes and its Co-morbiditiesHypertensionHypertension

Categories for Blood Pressure Levels in Adults (JNC VII)*

Blood Pressure Level (mmHg)

Category Systolic Diastolic

Normal < 120 And < 80

Prehypertension 120 -139 Or 80 – 89

High Blood Pressureg

Stage 1 Hypertension 140 - 159 Or 90 - 99

Stage 2 > 160 Or > 100Hypertension > 160 Or > 100

When systolic and diastolic blood pressures fall into different categories, the higher category should be used to classify blood pressure level. For example,

* Aged 18 years or older

160/80 mmHg would be stage 2 hypertension (high blood pressure)

Diabetes Is a Major Multiplier of Cardiovascular Risk in Patients With HypertensionypSystolic Blood Pressure and Cardiovascular Mortality

Diabetes

No Diabetes

245250

rs

Diabetes

130

153160

150

200

rM

ort

ality

Pers

on

-Yea

130

85

62

112

7355

100

rdio

vasc

ula

rP

er

10

,00

0

42

2218

55

0

50Car

Rate

P

Stamler J, et al. Diabetes Care. 1993;16:434–444.

120 - 139<120 >200

Systolic Blood Pressure mm/Hg

160 -179 180 - 199140 -159

Major Outcomes of the Hypertension Optimal T t t (HOT) T i lTreatment (HOT) TrialDiabetes Sub-group shows that lowering blood pressure is beneficial for diabetes patients with hypertension

30

<85 mmHG (n 501)

<90 mmHG (n=501)

Diastolic Target

24

1820

25

Pt-

Years

<85 mmHG (n=501)

<80 mmHG (n=499)

11

8

111110

15

ven

ts/

10

00

433

0

5

Ev

Hansson L, et al. Lancet. 1998;351: 1755-1762.

CV MortalityMIMajor CV Events

Effect of Blood Pressure Control in the UKPDSTight vs. Less Tight ControlTight vs. Less Tight Control

1,148 Type 2 patients

A BP l d t 144/82 H ( t l 154/87) Average BP lowered to 144/82 mmHg (controls: 154/87);9-year follow-up

Any diabetes-related endpointDiabetes related deaths

Tight Control

2432

Risk Reduction (%) P value

0.00460 019Diabetes-related deaths

Heart failureStroke

325644

0.0190.00430.013

Myocardial infarctionMicrovascular disease

2137

NS0.0092

UKPDS Group. BMJ. 1998;317:703-713.

UKPDS hypertension sub-study: Tight blood pressure control reduces complications in diabetespressure control reduces complications in diabetes

Stroke20

44% i k d ti

%)

Diabetes-related deaths40

32% i k d ti%)

15

10

44% risk reduction P = 0.013

s w

ith e

vent

s (

30

20

32% risk reduction P < 0.02

with

eve

nts

(%

Years

0

5

30 5 7 86421 9

Patie

nts

Years

0

10

30 5 7 86421 9Patie

nts

Tight control with captopril or atenolol:

Microvascular disease

nts

(%)

20

15

37% risk reduction P < 0 01

Less tight control: mean BP 154/87 mmHg

Tight control with captopril or atenolol: mean BP 144/82 mmHg

ents

with

eve

n 15

10

5

P < 0.01

UKPDS Group. BMJ. 1998;317:703-713.

Years

Pati

030 5 7 86421 9

Chobanian AV et al. JAMA. 2003;289:2560-72

Most relevant drugs are indicated for hypertension patients with diabetespatients with diabetes

Chobanian, et al.2004

ADA Recommendations on Hypertension

Systolic Blood Pressure <130 mmHG however depending

GOAL

Systolic Blood Pressure <130 mmHG, however depending on patient charecteristics and response to therapy, higher

or lower SBP targets may be appropriate

SBPor DBP

130 – 139 mmHG80 – 89 mmHG

SBPor DBP

> 140 mmHG> 90 mmHG

• Should receive • Lifestyle therapy alone for

a maximum of 3 monthspharmacological therapy in addition to lifestyle therapy

• If targets are not achieved, start treatment with pharmacological agents

Diabetes Care 2012; 35 (Suppl. 1): p29

Years

ADA Recommendations on Hypertension Cont.

Lifestyle Treatment Pharmacological Treatment

• Weight Control

• Increased consumption of fruit, vegetables and low

• Pharmacologic therapy

• A regimen that includes either an ACE I or ARBfruit, vegetables and low

fat diet

• Sodium restriction

• Increased physical

an ACE I or ARB

• If one class is not tolerated, the other should be substituted

• Other classes but RAS are• Increased physical activity

• Alcohol moderation

• Other classes but RAS are equally good.

• Multiple drugs are generally required

• If ACE I, ARBs, or diuretics are used:

• Monitor: kidney function and

Diabetes Care 2012; 35 (Suppl. 1): p29

s-potassium

Dyslipidemia

Mean Plasma Lipids at Diagnosis of Type 2 DiabetesUKPDSUKPDS

MEN WOMEN

Number of Pts

Type 2 Control

MEN

2139 52

Type 2 Control

WOMEN

1574 143Number of Pts

TC (mg/dl)

C ( /dl)

2139

213

39

52

205

32

1574

224

*

143

217

3LDL-C (mg/dl)

HDL-C (mg/dl)

139

39**

132

43

151*

43*

135

55

TG (mg/dl) 159* 103 159* 95

* P<0.001, ** P<0.02 comparing type 2 vs. control group

UKPDS Group. Diabetes Care 1997;20:1683-1687.

A Guide to Selecting Treatment

BMI (kg/m2)

T t t 25 26 9 27 29 9 30 34 9 35 39 9 ≥40Treatment 25 – 26.9 27 – 29.9 30 – 34.9 35 – 39.9 ≥40

Diet, exercise, and behavior therapy

With comor-biditi

With comor-biditi

+ + +be a o t e apy

bidities bidities

PharmacotherapyWith

comor-biditi

+ + +bidities

Bariatric surgeryWith

comor-biditi

+bidities

NIH/NHLBI, NAASO. The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. 2000.

Heart Protection StudyProportions of patients with major vascular events in the Heart p p jProtection Study (HPS) by year of follow-up evaluation and numbers of events prevented with simvastatin treatment per 1,000 individuals

The American Journal of Cardiology, Volume 92, Issue 4, Supplement 2, 21 August 2003, Pages 3–9

Meta-analysis of statin treatment in diabetes

Risk reduction of clinical outcomes per 40 mg/dL (1.0 mmol/L) reduction in LDL cholesterol• 21% reduction major vascular events• 25% reduction in coronary revascularisation• 25% reduction in coronary revascularisation• 21% reduction in stroke

• 9% reduction in all-cause mortality• 9% reduction in all-cause mortality • 13% reduction in CVD mortality• No difference in non-vascular mortality

Independent of baseline LDL or prior CVD

Lancet, 371, 117-25, 2008

Order of Priorities for Treatment of Diabetic Dyslipidemia in AdultsDyslipidemia in Adults

1

• First choice: HMG CoA reductase inhibitor (statin)

LDL Cholesterol Lowering

First choice: HMG CoA reductase inhibitor (statin)

• Second choice: Bile acid binding resin or fenofibrate

2 HDL cholesterol raising

• Behavior interventions such as weight loss, increased physical activity and smoking cessation

• Glycemic control

• Difficult except with nicotinic acid, which is relatively contraindicated, or fibrates

Triglyceride lowering3

• Glycemic control first priority

• Fibric acid derivative (gemfibrozil, fenofibrate)

• Statins are moderately effective at high dose in

Adapted from American Diabetes Association. Diabetes Care 2000;23(suppl 1):S57-S60.

Statins are moderately effective at high dose in hypertriglyceridemic subjects who also have high LDL cholesterol

Updated ATP III LDL-C Goals and Cutpoints for Therapy

Risk Category

LDL-C (mg/dL)

GoalInitiation Level for

Consideration Level for DrugGoal Level for

TLCLevel for Drug

Therapy

High risk: CHD or CHD risk equivalents

<100 (optional:

100 100(<100: consider drug CHD risk equivalents

(10-yr risk >20%) <70) options)

Moderately high risk: 2+ risk factors

<130 (optional:

130 130(100–129: consider risk: 2+ risk factors

(10-yr risk 10–20%)

( p<100) drug options)

Moderate risk:2+ risk factors

<130 130 160

2+ risk factors(10-yr risk <10%)

Lower risk:0–1 risk factor

<160 160 190 (160–189: LDL-C–

Grundy SM et al. Circulation 2004;110: 227-239

(lowering drug

optional)

Conclusions on Statins

• Statin therapy should be considered for all individuals with type 2 diabetes• independent of baseline lipid levels if previously CVDp p p y

• Statin therapy should be considered for all patients above 40 y with more than 1 risk factor

• Especially if• Especially if • Prior CVD• Albuminuria• Smokers• Smokers• Hypertension• Severe family history

• Lack of data for age < 40y• Lack of data for age < 40y

• Should be considered in type 1 diabetes at high risk of CVD or with signs of diabetic complications

ADA 2012

Fibrates

• Greater reductions in triglycerides

• Increase HDL cholesterol more effective than statins

• Combined treatment (fibrates + statins) decrease

triglycerides and LDL cholesterol and increase HDL

cholesterol more than statins or fibrates as

monotherapymonotherapy

• However, the combination of fenofibrate and

simvastatin does not reduce the rate of fatalsimvastatin does not reduce the rate of fatal

cardiovascular events, nonfatal MI, or nonfatal stroke,

as compared with simvastatin alone

Nicotonic Aid

• Significant reduction in triglycerides and increases HDL compared to fibrates and statinsHDL compared to fibrates and statins

• Significant effects in combination with statins on Intima Media Thickness (proxy marker of atherosclerosis) compared to statins alone

• Adverse effects: vasodilatation (flushing), increases HbA increase uric acidHbA1c, increase uric acid

• No data on Nicotinic acid on CVD endpoints

Efficacy of Multiple Risk Factor Intervention in High-Risk Subjects (Type 2 Diabetes with Microalbuminuria)j ( yp )The STENO 2 Study

, (%

)

72

58

71

6360

70

80

ng Mean

7.8

y,

5151

30

40

50

en

ts R

each

in

en

t G

oals

at

162021

410

20

30

Pati

e

ive-T

reatm

e

0Glycosylated hemoglobin

<6.5%

Diastolic BP <80 mm/HgIn

ten

si

Treatment Endpoints

Systolic BP <130 mm/Hg

Triglycerides >150 mg/dl

Cholesterol <175 mg/dl

Gæde P et al. N Engl J Med 2003;348:383-393

p

Intensive Therapy

Conventional Therapy

Primary Composite Cardiovascular EndpointSTENO 2 StudySTENO 2 Study

85 CVD events in 35 ’conventional’ patients (44%) 33 CVD events in 19 ’intensive’ patients (24%)

0 5

0,6

Conventional

Probability for primary endpoint

0,3

0,4

0,5

0,1

0,2

0,3

Intensive

0,0

1 2 3 4 5 6 7 80

Years of follow up

Hazard ratio 0.47 (0.24 to 0.73); p=0.007

Gæde P et al. N Engl J Med 2003;348:383-393.

Years of follow-up

LECTURE

Non-pharmacologyIntervention

Non-Pharmacology Intervention

Lecture:gy

30 minutes

Non-Pharmacology InterventionLectureLecture


• The relationship between nutrition and blood glucose control

• Understand the eating pattern in the local region that could play a role on the fat or carbohydrate intake

• Determine healthy and unhealthy eating and initiating• Determine healthy and unhealthy eating and initiating and assessing dietary intervention in a clinical setting

• Understand the importance of exercise and the relationship between exercise and blood glucose control

• Understand the relationship between smoking and diabetes associated complicationsdiabetes associated complications

Something went wrong…Something went wrong…

2.5 million years 50 years

Diet & Exercise in DiabetesDiet & Exercise in Diabetes

• Important in type 1 and type 2 diabetes

• In type 2 diabetes:• Obesity and physical inactivity are major risk factors• Diet and exercise may provide good long-term• Diet and exercise may provide good long term

glycaemic control in some patients

• Improved cardiovascular status

• Cost-effective

Medical Nutrition Therapy in DiabetesMedical Nutrition Therapy in Diabetes

As integral part of : g p

• Prevention and management of diabetes

• Component of diabetes education

• Prevention of diabetes complication

Source: Diabetes Care, Vol. 31, Suppl. 1, 2008

Targets of Medical Nutrition Therapy in prevention d t f T 2 Di b tand management of Type 2 Diabetes

Individual with Diabetes Risk-factors or with pre- Individual with diagnosed

diabetes Diabetes

1) To reduce the risk of diabetes and cardiovascular

1) To achieve and maintain:

• Blood Glucose levels in the normaldisease by promoting healthy food choices and physical activity leading to

Blood Glucose levels in the normal range

• A lipid profile that reduces the risk for vascular diseases

moderate weight loss that is maintained.

• Blood Pressure levels in the normal range

2) To prevent / delay progressivity of chronic complicationsp

3) To address individual nutrition needs, taking into account personal and cultural preferences and willingness to change

Diabetes Care, Vol. 31, Suppl. 1, 2008

change

The Fundamentals of food management for di b t ti tdiabetes patients

Similar with healthy people:B l f d i t k di t l i d t iti d f• Balance food intake according to calories and nutrition needs for each individual

• Weight loss, increased physical activity, and weight management

C i t i d t d b h d t i t k t l d• Consistency in day-to-day carbohydrate intake at meals and snacks

• Nutritional content

• Timing of meals and snacks

• Carbohydrates are the principal determinant for blood glucose

Emphasis (‘triple Js)’:• Jadwal (Schedule)

• Jenis (Type)• Jenis (Type)

• Jumlah (Amount)

The relationship between healthy nutrition and bl d lblood glucose

DSE: Usual Diabetes Care

ILI I t i Lif t l I t ti

Source: Long-term Effects of a Lifestyle Intervention on Weight and Cardiovascular Risk Factors in Individuals with Type 2 Diabetes; Four Yesr Results of the Look AHEAD Trial. The Look AHEAD Reseach Group

ILI: Intensive Lifestyle Intervention

Guidelines for a healthy dietPERKENI 2011PERKENI 2011

• Healthy balanced diet composed of:

Fat

• 45-65% carbohydrate

• 20-25% fat• 20 25% fat

• 10–20% protein

Carbohydrate iCarbohydrate Protein

The Indonesian Food Pyramid

http://www.fagnutrition.com

Carbohydrate

Eat Less of These Eat More of These

Fruit Low fat Milk BeansWhite sugar Brown sugar Fruit, Low fat Milk, Beans, Brown rice, Yoghurt, Whole wheat bread

White sugar, Brown sugar, White bread, White rice,

Proteins


Chicken Fish TofuSausages processed meat Chicken, Fish, TofuSausages, processed meat, Shrimps and shell fish, Red Meat

Fat


Avocado Nuts Olives Oils rich inCoconut Margarine/butter Avocado, Nuts, Olives, Oils rich in poly and mono unsaturated fats

Coconut, Margarine/butter, Cheese, Oils/fats rich in saturated fat

How you cook is importantHow you cook is important

Less Healthy More Healthy

Understanding portion sizes is importantRecommendation to take smaller portion sizes of the less

frecommended food

Rice boiled – 100 gCalorie – 175 kcal

Carbohydrates – 40gm

Rice boiled – 200 gCalorie – 350 kcal

Carbohydrates – 80gm y gy g

Noodles boiled – 200 gmCalorie – 175 KcalCarbohydrates – 40 gmy g

Source: Daftar Bahan Makanan Penukar

The relationship between exercise and blood glucoseg

Both resistance and aerobic exercise were effective in reducing blood glucose levels and HbA1c levels

HbA1c values collected 12 weeks prior to the initiation of the exercise program(Baseline), at the start of the exercise program (Pre-Intervention) and at the completionof the 10 weeks program (Post-Intervention). Ten week changes are denoted by * (p <0 05) A difference between exercise groups is denoted by # (p < 0 008)

Diabetology & Metabolic Syndrome, 2009, 1:27

0.05). A difference between exercise groups is denoted by # (p < 0.008).

Exercise significantly reduces HbA1c

Pooled meta-analysis of 14 exercise trials

%

0 0

0.1

0.2

Exercise

vention

nce

)

0.08%

-0.2

-0.1

0.0Non-exercise control

in H

bA

1c

post

-inte

rvea

n d

iffe

ren

-0 5

-0.4

-0.3

Chan

ge

bas

elin

e to

w

eighte

d m

e

p<0.001

Effect was

-0.66%-0.7

-0.6

0.5

from

(w weight-

independent

Boulé NG, et al. JAMA 2001;286:1218-27.

Source: Boule NG et al. Effects of exercise on glycemic control and body mass in T2 Diabetes: JAMA2001; 286:1218-27

Diabetes and SmokingBackground

‘Before’ diabetes

• Smoking is associated with insulin resistance• dose-response relationship between smoking and the risk

of type 2 diabetes• Stopping to smoke decreases the risk of type 2 diabetes

‘Additional’ to diabetes

• Smoking increases the risk of developing diabetic complications - nephropathy, neuropathy and retinopathy

• Independent risk factor for CVD and all-cause mortality• Smokers are also lipid intolerantSmokers are also lipid intolerant• Smoking cessation increases HDL and reduces LDL levels,

despite weight gainF hi i F S t l L t (1992) 339 (8802) 1128 1130 Al D l i WK t l A h I t M dFacchini. F. S et al Lancet, (1992) 339 (8802) , pp. 1128-1130 . Al-Delaimy WK, et al. Arch Intern Med. 2002;162(3):273-279. Patja, K., et al Journal of Internal Medicine, 258: 356–362. Chaturvedi N, Diabetes Care 1995; 18: 785–92.Jacobs DR Jr et al Arch Intern Med 1999;159: 733-40. Axelsen M., et al (1995), Journal of Internal Medicine, 237: 449–455.D.P. Mikhailidis, et al (1998) The Journal of the Royal Society for the Promotion of Health 118: 91

Significant reduction in mortality of diabetes ti t kpatients among non-smokers

Non-diabetic womanDiabetic woman

1,9842,000

rson-y

ears

) Diabetic woman

1,443

1,2191,249

1,0121,000

1,500

100.0

00 p

er

591

368323275215

500

,

Rat

e (p

er 1

215

0

Mort

ality

Past 1-14 cig / dayNever 15-34 cig / day

35+ cig / day

Source: Wael K. Al-Delaimy et al. Diabetes Care 24: 2043-2048, 2001

cig = cigarette

G Di iGroup Discussion

Practical Initiation of Diet Programs for diabetes patientspatientsFood Mapping Systems

Food Mapping System can be used for patient education to increase patient compliance with diet scheme

Beras Merah Kukus

Nasi Putih Nasi Goreng

A B k A G Ayam GorengAyam Bakar Ayam Goreng Ayam Goreng Tepung

Ikan Bakar / Kukus Ikan Goreng Udang GorengKukus

Sayur Kukus Kukus Dim Sum Dim Sum Goreng

Practical Initiation of Diet Programs for diabetes patientsHealthy Plate Models

Portion Control Plate was effective in inducing weight loss and decreased use of hypoglycemic medications in obese patients with type 2 diabetes mellitus

Carbo-hydrate /

Starch

Protein

Vegetables

Protein

Carbo-hydrate /

StarchVegetables

T-shaped plate model to loose

Y-shaped plate model tomodel to loose

weightmodel to

maintain weight

Pedersen DE et al. Arch Intern Med. 2007; 167

Practical Initiation of Exercise Programs for diabetes patientsdiabetes patientsCRIPE Pricnciple

CRIPE: Continuous Rhytmic Interval Progressive EnduranceCRIPE: Continuous, Rhytmic, Interval, Progressive, Endurance

Continuous • Exercises should be done continuously without Continuous rest (e.g. 30 minutes of jogging without rest)

Rhythmic• Choose more rhythmical sports where regular

contraction and relaxation are possible (e.g. walking, jogging, running and swimming)walking, jogging, running and swimming)

Interval • Exercises with both quick and slower actions (e.g. running followed by jogging)

Progressive • Increase intensity according to abilities (heart rate target: 75-85% from maximum heart rate)

Endurance• Exercise for endurance to improve

cardiorespiratory abilities (e g walkingEndurance cardiorespiratory abilities (e.g. walking, jogging, swimming, cycling)

LECTURE

Diabetes AcuteComplications-

Hypoglycemia and DKA

Diabetes Acute Complications – Hypoglycemia and DKA

Lecture:Diabetes Acute Complications Hypoglycemia and DKA

30 minutes

Management of HypoglycemiaLecture


• Understand the hypoglycemia mechanism and how hypoglycemia should be treated

• Understand how to adjust OAD - or insulin dosage after• Understand how to adjust OAD - or insulin dosage after hypoglycemic events

• Understand what causes a DKA event, how DKA is treated and what to do if you experience a patient with DKA

What is hypoglycemia?

neurogenic symptoms due to low plasma glucose levelsA state of neuroglycopenic and/or neurogenic

symptoms due to low plasma glucose levels

• Low plasma glucose levels defined as:

• ≤70 mg/dL (ADA)1≤70 mg/dL (ADA)

• <60 mg/dl (PERKENI)2

• <72 mg/dL (CDA)3g/ ( )

• Symptoms respond to the administration of carbohydrate3

1 ADA Di b t C 2005 28 1245 9 2 PERKENI K 2011 3 Y l t l C di J

ADA, American Diabetes Association; CDA, Canadian Diabetes Association;

1. ADA. Diabetes Care 2005;28:1245–9; 2. PERKENI Konsensus 2011. 3. Yale et al. Canadian J Diabetes 26:22–35

Why address hypoglycemia in diabetes training

• Reducing HbA1c levels associated with prevention or delay in complications and death

• Hypoglycaemia is a limiting factor in achieving glycaemic targets

• Hypoglycaemia is associated with morbidity and rarely even be fatal

• Optimising glycaemic control is of obvious importance:• Optimising glycaemic control is of obvious importance:

• $465 billion USD spent to treat diabetes and its complications in 2011; hypoglycaemia is cost-intensive

• 6.8% of global all-cause mortality attributed to diabetes in 2010 (4 million deaths)

Cryer et al 2003. Diabetes Care; 26,6: 1902-1912. IDF Diabetes Atlas tth ed., 2009. Roglic and Unwin 2010. Diabetes Research and Clinical Practice; 87: 15-19

Most common symptoms of Hypoglycemia

Blurred visionWeakness

Sweating

Slurred speech

HungerPalpitations

WeaknessTremor

Circumoral paraesthesiaHunger

Vertigo

fHeadache

Cold feelingAnxiety

EuphoriaNausea

Patients (%)

Difficulties in concentration

0 20 40 60 80 100

Patients (%)

Pramming 1991

Sequel of hypoglycaemiaSequel of hypoglycaemia

• Mild symptomatic hypoglycaemia N di t i li i l ff t• No direct serious clinical effects

• May impair subsequent hypoglycaemia awareness

• Severe hypoglycaemia associated with• Stroke and transient ischaemic attacks• Memory loss/cognitive impairment• Memory loss/cognitive impairment• Myocardial infarction• Injury (direct/indirect)• Death

Turner et al. (UKPDS 33), 1998. The Lancet; 352: 837-853

Risk Factors of Hypoglycemia

• General risk factors for hypoglycaemia:1,2

• delayed or missed meal

• consuming a smaller meal than plannedg p

• exercise

• use of diabetes medications

• drug/alcohol consumptiondrug/alcohol consumption

• increased insulin sensitivity or decreased insulin clearance

• Risk factors for major hypoglycaemia:3,4

/d ti f di b t t t t• age/duration of diabetes treatment

• intensive glycaemic control

• hypoglycaemia unawareness• sleep

• antecedent hypoglycaemia

• history of major hypoglycaemia

1.Briscoe & Davis. Clin Diabetes 2006;24:115–21; 2. ADA Workgroup on Hypoglycemia. Diabetes Care 2005;28:1245–9. 3. Frier. Diabetes Metab Res Rev 2008;24:87–92; 4. Cryer. Diabetes 2008;57:3169–76

Hypoglycaemic events occur more often in Type 1 diabetes patients and are less frequent and less severe in Type 2 diabetes patients both on conventional and intensive therapy

ears

Conventional Therapy

90

100

DCCT (T1 DM) ears

Intensive Therapy

90

100

DCCT (T1 DM)

00 P

atie

nt

Ye

50

60

70

80 ACCORD (T2 DM)

00 P

atie

nt

Ye

50

60

70

80 ACCORD (T2 DM)

ents

per

10

20

30

40

50

ents

per

10

20

30

40

50

Eve

b (%)

0

10

6.0 6.5 7.0 7.5 8.0 8.5 9.0

Eve

b (%)

0

10

6.0 6.5 7.0 7.5 8.0 8.5 9.0

Adapted from DCCT Research Group. Diabetes 1997. Adapted from Bonds D., data presented at ADA 2009

HbA1c (%) HbA1c (%)

Prevention of Hypoglycemic Events

• Education

• Symptoms

• Self management

• Proper food intake in therapy

R titi d ti i ti t ith d d iti• Repetitive education in patients with decreased cognitive function

• Self monitoring blood glucose (SMBG)

• Exercise planning

• Measuring blood glucose before exercise

• Consuming carbohydrate• Consuming carbohydrate

• Adjust insulin dose based on the blood glucose level

• Right type and dose for therapy

Treatment of mild Hypoglycemia

Treating early signs

First: 10–20 g fast-acting carbohydrate, e.g.:• 3–6 glucose tablets

• 90 180 ml fizzy drink or squash (ex: coke drink bottle• 90–180 ml fizzy drink or squash (ex: coke drink, bottle tea not diet)

• Two teaspoons of sugar added to a cup of cold drink

50 100 l d i k• 50–100 ml energy drink

Then: • If next meal is due add extra carbohydrate• If next meal is due, add extra carbohydrate

• If next meal is not due, eat longer-acting carbohydrate, such as biscuits or a sandwich

RCN 2004

Treatment of moderate-to-major HypoglycemiaTreatment of moderate to major Hypoglycemia

Treating late signs

Patient requires assistance with treatmentIf conscious:

Treating late signs

• Carer should help the patient to consume 10–20 g fast-acting carbohydrate

• Dextrose gel may be useful

fIf unconscious: • Don’t put anything in patient’s mouth

• IM or SC glucagon or IV glucose should be d i i t dadministered

• Emergency services should be called

IM: intramuscular SC: subcutaneous IV: intravenous

RCN 2004; Cryer 2010

IM: intramuscular, SC: subcutaneous, IV: intravenous

Adjusting Dosage after a Hypoglycemic EventAdjusting Dosage after a Hypoglycemic Event

If hypoglycemic events are

repeated OAD and / or Insulin

OAD: Depending on drug

repeated, OAD and / or Insulin

dosages should be reducedInsulin: Initially decrease

with 2 units / day

Di b t K t id iDiabetes Ketoacidosis

What is Diabetes KetoacidosisWhat is Diabetes Ketoacidosis

Acute decompensated metabolic state due to

severe insulin deficiency severe insulin deficiency

over-activity of glucagon & other counter-regulatory hormone

Common in Type 1; Rare in Type 2

Potentially life-threatening

High mortality

Incidence : 5-8 /1000 diabetic persons/yr

Mortality rates 9-14 % - Has improved with insulin use 2%

Watkins et al. In: Diabetes and its Management 2003

Why are patients developing ketoacidosisWhy are patients developing ketoacidosis

The most common events that cause a person with diabetes to develop diabetic ketoacidosis are:diabetes to develop diabetic ketoacidosis are:

infection such as diarrhea, vomiting, and/or high fever (40%)

missed or inadequate insulin (25%)

newly diagnosed or previously unknown diabetes newly diagnosed or previously unknown diabetes (15%)

Various other causes may include a heart attack, stroke trauma stress alcohol abuse drug abusestroke, trauma, stress, alcohol abuse, drug abuse, and surgery.

Approximately 5% to 10% of cases have no identifiable cause

How to Diagnose Diabetes KetoacidosisHow to Diagnose Diabetes Ketoacidosis

Symptoms Signs

Anorexia

Nausea

Tachycardia

Hypotension

Vomiting

Thirst

Hypotension

Hypothermia

Impaired consciousness Thirst

Polyuria

Weakness

Impaired consciousness

Warm dry skin

Weakness

Abdominal pain

Weight loss

Kussmaul respiration

Acetone odour on breath Weight loss

Diabetes Ketoacidosis DefinitionsDiabetes Ketoacidosis Definitions

DKA is defined as:

Increase serum concentration of ketones greater than 5 mEq/L (beta hydroxybutirate acid > 0,6)

Blood glucose level greater than 250 mg/dL(although it is usually much higher),

Blood pH less than 7 3 Blood pH less than 7.3

Ketonemia and ketonuria are characteristic, as is a serum bicarbonate level of 18 mEq/L or less (< 5 mEq/L is indicative of severe DKA)

Diabetes Care, Vol. 29, Number 12, December 2006

Objectives and Management of DKA Treatment

S h &li bl d

Objectives Management

1. Search & treat precipitating cause

2. Insulin iv (rapid / short-

1. To normalize blood glucose as soon as possible with Insulin

( p /acting)

3. Replacing fluids

2. To replace fluids and reverse ketoacidosis

3 Monitoring:4. Replacing electrolytes -

potassium & magnesium- if required

3. Monitoring:

• Vital signs

Fluid and electrolyte

5. For GPs: If you observe a DKA case, immediately send the patient to the

• Fluid and electrolyte balance

• Glycaemia send the patient to the hospital

Initial DKA Treatment in Primary Care

1. Evaluate vital signs and urine volume

2. IV line, start the rehydration Prepare the patient

3. Check the blood glucose periodically (per hour if possible)

for Hospital

12:00 12:30 1:00 2:00

30 min. 30 min. 60 min.

• Start insulin with bolus IV 180 mU/kgBW and continue with insulin dripStart insulin with bolus IV 180 mU/kgBW, and continue with insulin drip 90 mU/hour/kgBW

• Check blood glucose per hour with glucometer on the way to hospital

Diabetes Acute Complication – Hypoglycemia and DKALecture

Main Learning PointsMain Learning PointsSummarySummary

• Understand the hypoglycemia mechanism and how hypoglycemia should be treated

• The risk of hypoglycemia is one of the key limiting factors in reaching optimal glucose targets

• For Insulin hypoglycemia is mainly a should be treated

• Understand how to adjust OAD - or insulin dosage after hypoglycemic events

• For Insulin, hypoglycemia is mainly a phenomenon occurring in Type 1 diabetes patients

• Prevention of hypoglycemia requires d f bl d

• Understand what causes a DKA event, how DKA is treated and what to do if you experience a patient

patient education, frequent blood glucose monitoring and exercise planning

• If hypoglycemia occur repeatedly, you experience a patient with DKA

yp g y p y,reduce the dosage of OAD and/or Insulin

• DKA should be regarded as an emergency situation and promptemergency situation and prompt treatment with insulin is vital

LECTURE

Initiating DiabetesTreatment with OADs

Initiating Diabetes Treatment with OADs

Lecture:g

30 minutes

Initiating Diabetes Treatment with OADsLectureLecture


• Understand the different classes of OADs and when to use which OADs – either as monotherapy or in pycombination with other OAD’s / Insulin

Factors to Consider when Choosing an Anti-hyperglycemic agenthyperglycemic agent

Effectiveness in lowering glucose

Extraglycaemic effects that may reduce long-term complications

Safety profile

TolerabilityTolerability

Cost

Effect on body weight

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

Treatment therapies for Type 2 diabetesWh d HWhen and How to start treatment


Lifestyle + Metformin

+-other OAD or GLP-1 agonists

Basal

Basal Insulin

Premix Insulin

Basal + Bolus

Insulinagonists

HbA ≥7 0%

Insulin

HbA1c ≥7.0%


Updated PERKENI Type 2 Diabetes Treatment AlgorithmAlgorithm

Diabetes STEP 1 STEP 2 STEP 3

Healthy life style Healthy life style +

Mono therapy Healthy life style py+

2 OADCombination

Healthy life style +

Combination 2 OADAlternative option, if :

Note:

1. Therapy failed if target of HbA1c < 7% is not achieved

i hi 2 3 h +Basal insulin

p ,

• No insulin is available

• The patient is objecting insulin

• Blood glucose is still not optimally controlled

within 2-3 months for each step

2. In case of no HbA1ctest, the use of blood glucose level

Insulin Intensification*

Healthy life style +

3 OAD Combination

optimally controlledis also permitted. Average blood glucose level for a few BG test in one day can be converted to HbA1c

*Intensive Insulin: use of basal insulin together with insulin prandial

converted to HbA1c(ref: ADA 2010)

Main pathophysiological defects in type 2 DM

pancreatic insulinsecretion

incretineffect

PancreasIntestinesBrain

pancreatic glucagonsecretion

gut? Kidney

gutcarbohydratedelivery andabsorption Hyperglycemia

Muscle

Glucose reabsorpsion

peripheralglucose uptake

LiverMuscle

hepatic glucose production

uptake

Adipose

Adapted from:Inzucchi SE, Sherwin RS. Diabetes Mellitus. In: Goldman L, Ausiello D, eds. Cecil Textbook of Medicine. 23rd Edn. Philadelphia, Pa: Saunders Elsevier; 2007.

Current available OADs and non-Insulin injectablesin Indonesiain Indonesia

• Metformin• Sulfonylureas (SUs) and glinides• Sulfonylureas (SUs) and glinides• α-glucosidase inhibitors (AGIs)• Glucagon-like peptide-1 (GLP-1) agonistsGlucagon like peptide 1 (GLP 1) agonists• Thiazolidinediones (TZDs)• Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors)

Primary sites of action of currently available oral anti-diabetic agents and non-insulin injectablesanti diabetic agents and non insulin injectables

MuscleBlocks

P t

Adipose

LiverMetformin

TZD

FFAl

Promotes

Circulatory System

Glucose

release

TZD

Metformin

Pancreas

FFA

Insulinrelease

AGI

Glucoseabsorption

Intestinal lipase inhibitor

Fat

Intestines

GLP-1 agonist

CarbohydratesDPP-4inhibitor

Cheng A, Fantus G. Can Med Assoc J 2005;172:213–26.. Barnett A. Int J Clin Pract 2006;60:1454–70. Pérez López G, et al. Nefrologia. 2010;30:618–25.

AGI: α-glucosidase inhibitors; DPP-4: dipeptidyl peptidase-4; FFA: free fatty acid; TZD: thiazolidinedione

MetforminMode of ActionMode of Action

The primary effects of metformin are to decrease hepatic glucose production and increase insulin-

mediated peripheral glucose uptake

Adipose tissueMuscle Liver Intestine

Anaerobic glucosemetabolism

Glucose uptake Glucose uptake

Glucose oxidation Glucose oxidation

Glycogenesis

Gluconeogenesis

Glycogenolysis

Oxidation of FA

Oxidation of FA

Krentz AJ Bailey CJ Drugs 2005;65:385 411

FA: Fatty Acids

Krentz AJ, Bailey CJ. Drugs 2005;65:385–411.

MetforminCli i l O i d C t i di tiClinical Overview and Contraindications

Metformin

S f tEfficacy*

Safety, Tolerability and Adherence

Contraindications Advantages

• HbA1c reduction • Associated with • Renal • Do not causeHbA1c reduction of 1-2%

• FPG reduction of 40-70 mg/dl

Associated with diarrhea and abdominal discomfort

Renal insufficiency

• Liver failure

• Heart failure

Do not cause hypoglycaemia when used as mono-therapy

• Latic acidosis if improperly prescribed

• Heart failure

• Severe gastrointestinal disease

therapy

• Do not cause weight gain; may contribute to weight loss


* Efficacy depends on existing blood glucose levels

MetforminTitrationTitration

Starting dose

850 mg daily or 500 mg daily or bid with

Starting dose

500 1000 d il

MET-XRMET-IR

850 mg daily or 500 mg daily or bid with breakfast and or dinner

500 mg or 1000 mg once daily with evening meal

Titration

After 5 to 7 days, advance dose to 850 mg bid or 1000 mg bid if GI side effects have not

occurred

Titration

Increase dose in 500 mg increments per week b d FPG d GI t l bilit

If GI side effects occur, decrease to previous dose and try to advance dose at a later time

based on FPG and GI tolerability

Maximum dose

850 mg bid or 1000 mg bid

Maximum dose

2000 mg qd with evening meal

1. Nathan DM, et. al. Diabetes Care, 2009;32:193–203. 2. Jabbour S, Ziring B. Postgraduate Medicine, 2011;123:15–23.

Bid: twice daily; FPG: fasting plasma glucose; GI: gastrointestinal; MET-IR: immediate release metformin; MET-XR: extended release metformin; qd: once daily.

MetforminLittle benefit – if any - to go above 2 000 mgLittle benefit if any to go above 2.000 mg

Fasting Plasma Glucose HbA1c

Metformin Dose Metformin Dose

0

10

l)

2500mg2000mg1500mg1000mg500mg

Metformin Dose

0.0

2500mg2000mg1500mg1000mg500mg

Metformin Dose

40 9

31.0

18.920

30

40lace

bo

(m

g/

d

0.9

0.5

1.0 Pla

ceb

o (

%)

61.9

40.9

50

60

70Ch

an

ge v

s. P

1.61.7

1.2

1.5

Ch

an

ge v

s.

77.980

Garber AJ, Am J Med 1997;102:491-7.

2.0

1.7

2.0

SUs and GlinidesMode of ActionMode of Action

• Sulfonylureas (SUs) and glinides increase endogenous insulin

Pancreatic β-cell

GlATP-sensitive

potassium channelgsecretion by binding to pancreatic β-cells and triggering a cascade of intracellular events1–3

Glucose uptake

potassium channel

SUs / glinides

Glycolysisrespiration

Glucokinase

ATP

• The mode of action of SUsand glinides is similar, but stimulation of insulin

ti i id dsecretion is more rapid and short-acting with glinides

• SU receptors are also found on other cells including the I li lon other cells, including the cardiac myocytes

Insulin releaseVoltage-gated

calcium channel

Ca2+

ATP = orange Ca2+ = light green

1. Gallwitz B, Haring H-U. Diabetes Obes Metab 2010;12:1–11. 2. Schuit FC, et al. Diabetes 2001;50:1–11. 3. Krentz AJ, Bailey CJ. Drugs 2005;65:385–411.

SU: sulfonylurea; GLUT: glucose transporter.

SUs and GlinidesClinical OverviewClinical Overview

Sulphonylurea Glinides

Efficacy*Safety, Tolerability and Adherence

Efficacy*Safety, Tolerability and Adherence

• HbA1c reduction of 1-2%

• FPG reduction of 40 70 mg/dl

• Associated with hypoglycaemiaand weight gain

• HbA1c reduction of 0.5-1.5%


• Associated with hypoglycaemiaand weight gain

• Frequent of 40-70 mg/dl g/

• PPG reduction of 75-100 mg/dl

qadministration (with every meal) is required.

Krentz AJ, Bailey CJ. Drugs 2005;65:385–411. Nathan DM, et al. Diabetologia. 2009;52:17–30. Rosenstock J, et al. Diabetes Care. 2004;27:1265–70.


q

;

Alpha glucosidase inhibitorsMode of ActionMode of Action

• Slow digestion of sucrose and starch and therefore delay absorptiontherefore delay absorption

• Slow post-meal rise in blood glucose

• Side effectsSide effects

• Flatulence, abdominal discomfort , diarrhoea

• As mono-therapy will not cause hypoglycaemia

• Hypoglycaemia when used with other medicine (e.g. a sulphonylurea)medicine (e.g. a sulphonylurea)

1. Gallwitz B, Haring H-U. Diabetes Obes Metab 2010;12:1–11. 2. Schuit FC, et al. Diabetes 2001;50:1–11. 3. Krentz AJ, Bailey CJ. Drugs 2005;65:385–411.

Alpha glucosidase inhibitorsClinical OverviewClinical Overview

Alpha glucosidase inhibitors

Efficacy* Safety, Tolerability and Adherence

• HbA1c reduction of 0.5-1% • Associated with flatulence,


• PPG reduction of 40-50

diarrhea and abdominal discomfort

• As mono-therapy will notcause hypoglycaemiamg/dl cause hypoglycaemia

• Frequent administration (with every meal) is required.required

Krentz AJ, Bailey CJ. Drugs 2005;65:385–411. Nathan DM, et al. Diabetologia. 2009;52:17–30. Rosenstock J, et al.


, y g ; , g ; ,Diabetes Care. 2004;27:1265–70.

Thiazolidinediones (TZDs)Mode of ActionMode of Action

Thiazolidinediones (TZDs) increase the sensitivity of muscle and adipose cells to insulin and suppressing hepatic glucose

production

Adipose tissue Muscle Liver

Glucose uptake Glucose uptake Gluconeogenesis

Fatty acid uptake

Lipogenesis

Glycolysis

Glucose oxidation

Glycogenolysis

Lipogenesis

*Inconsistent findings

Pre-adipocyte differentiation Glycogenesis* Glucose uptake*


TZD: Thiazolidinediones

ThiazolidinedionesClinical OverviewClinical Overview

Thiazolidinediones

Safety Tolerability ContraindicatioEfficacy* Safety, Tolerability and Adherence

Contraindications Advantages

• HbA1creduction

• Associated with weight gain and edema

• Liver disease, heart failure or

• Reduced levels of LDL-cholesterol

of 0.5-1.5%

• FPG reduction

g

• Contraindicated in patients with abnormal liver function

• Warnings regarding risk

history of heart disease

• Pregnancy and breast feeding

LDL cholesterol and increased level of HDL-cholesterol

of 20-55 mg/dl

• Warnings regarding risk of fractures

• May exacerbate or precipitate congestive heart failure

g


heart failure

Krentz AJ, Bailey CJ. Drugs 2005;65:385–411. Drug Class Review: Thiazolidinediones. Available at:http://pharmacy.oregonstate.edu/drug_policy/pages/dur_board/reviews/articles/TZD_ClassReview.pdf . Rizzo M, et al. Expert Opin Pharmacother. 2008;9:2295–303.

DPP-4 inhibitorsMode of ActionMode of Action

Increases and prolongs GLP-1and GIP effects on β-cells

Food intake

β-cellsDPP-4

inhibitor

Stomach Pancreas

Glucose-dependent insulin secretion

DPP-4Net effect:

Increases and prolongs

Stomach

GI tract

a c eas

Incretins (GLP-1 GIP)

DPP-4blood glucose

Increases and prolongsGLP-1 effect on α-cells

α-cells

Glucose-dependent glucagon secretion

(GLP-1, GIP)

DPP-4: dipetidyl peptidase-4; GI: gastrointestinal; GIP:glucose-dependent insulinotropic polypeptide; GLP-1: glucagon-like peptide

Intestine

* GIP does not inhibit glucagon secretion by α-cells

Drucker DJ et al. Nature 2006;368:1696–705. Idris I, et al. Diabetes Obes Metab 2007;9:153–65. Barnett A. Int J Clin Pract 2006;60:1454–70. Gallwitz B, et al. Diabetes Obes Metab 2010;12:1–11.

p p

DPP-4 inhibitorsClinical OverviewClinical Overview

DPP-4 inhibitors

Safety Tolerability andEfficacy* Safety, Tolerability and Adherence

• HbA1c reduction of 0.5-1%

FPG d ti f 20 /dl

• Generally well tolerated

L i k f h l i• FPG reduction of 20 mg/dl


• Low risk of hypoglycemia

• Not associated with weight gain

• Upper respiratory tract infection5 has been reported in clinical studieshas been reported in clinical studies

• Most require only once daily administration

Ahrèn B. Expert Opin Emerg Drugs 2008;13:593–607. Gallwitz B, et al. Diabetes Obes Metab 2010;12:1–11. Amori RE,


p p g g ; , ; ,et al. JAMA 2007;298:194–206. Saxagliptin, FDA’s Endocrinologic and Metabolic Drugs Advisory Committee Briefing Document for April 2009 Meeting: NDA 22-350. Available at: http://www.fda.gov/OHRMS/DOCKETS/ac/09/briefing/2009-4422b1-02-Bristol.pdf. (accessed Nov 2010). Aschner P, et al. Diabetes Care 2006;29:2632–7.

GLP 1 AgonistMode of ActionMode of Action

Glucagon-like peptide-1 (GLP-1) agonist activates the GLPreceptor in the pancreas. This increases insulin release fromreceptor in the pancreas. This increases insulin release from the pancreatic β-cells, while inhibiting glucagon release by

the pancreatic α-cells

Pancreas

• Glucose-dependent insulin biosynthesis and secretion

• β-cell proliferationβ-cells

α cell

Pancreas

• Glucagon secretion

GLP-1 agonist Net effect: blood glucose

GLP-1: glucagon-like peptide

α-cell Glucagon secretion• β-cell apoptosis

1. Doyle ME, Egan JM. Pharmacol Ther 2007;113(3):546–93.

GLP 1 AgonistClinical OverviewClinical Overview

DPP-4 inhibitorsSafety Tolerability andEfficacy* Safety, Tolerability and Adherence

• HbA1c reduction of 1-2%


• Associated with moderate and transient nausea, vomiting and • FPG reduction of 6 12 mg/dl


, gdiarrhea

• Low risk of hypoglycemia and no evidence of increased CV risk

A i t d ith i ht d ti• Associated with weight reduction

• Associated with reduction in BP

Garber AJ. Diabetes Care 2011;34 (Suppl 2):S279–84. Moretto TJ, et al. Clin Ther 2008;30:1448–60. Drucker DJ. Cell Metab 2006;3:153–65. Amori RE, et al. JAMA 2007;298:194–206.


The Principles of OAD Combination Theory

• Two (or more) oral blood glucose-lowering medicines that have different mechanisms of action

• Two medications is better rather than increase i i iti l di i t i din initial medicine to maximum dosage

• Fewer side effects than mono-therapy at higher dosesdoses

Diabetes in elderly people

• Always start with the lowest dose

Remember the possibility of

of any blood glucose-lowering medicine and increase gradually

• Using shorter-acting medicines that reduces the risk of

• Forgetfulness

• Poor motivation

• Depressionthat reduces the risk of hypoglycaemia

• Hypoglycaemia may increase the risk of falls and heart attack in

• Depression

• Cognitive deficits

• Poly-pharmacy

older people • Reduced manual dexterity

• These factors impact on the ability to maintain self-care and achieve maximum benefits from bloodmaximum benefits from blood glucose-lowering medicines.

OAD’s – a quick summary of the different mechanism of actionsmechanism of actions

ThiazolidinedionesIncrease glucose uptakeThiazolidinedionesIncrease glucose uptake

Incretins :GLP-1 analogue(exen- atide)/DPP-4 inhibitors Improves glucose

Incretins :GLP-1 analogue(exen- atide)/DPP-4 inhibitors Improves glucose Increase glucose uptake

in skeletal muscle and decrease lipolysis in adipose tissue

Increase glucose uptake in skeletal muscle and decrease lipolysis in adipose tissue

inhibitors Improves glucose-dependent insulin secretion from pancreatic β-cells, suppresses glucagon secretionfrom -cells, slows gastric

inhibitors Improves glucose-dependent insulin secretion from pancreatic β-cells, suppresses glucagon secretionfrom -cells, slows gastric

MeglitinidesMeglitinides

from cells, slows gastric emptyingfrom cells, slows gastric emptying

SulfonylureasSulfonylureas

Increase insulin secretion from pancreatic -cellsIncrease insulin secretion from pancreatic -cells

-Glucosidaseinhibitors-Glucosidaseinhibitors

SulfonylureasIncrease insulin secretion from pancreatic -cells

SulfonylureasIncrease insulin secretion from pancreatic -cells

Delay intestinal carbohydrate absorptionDelay intestinal carbohydrate absorptionGLP = glucagon-like peptide.

Adapted from Cheng and Fantus. CMAJ. 2005;172:213–226.

Properties of available glucose-lowering agents that may guide treatment choice in Type 2 Diabetes

Class Compounds(s) Cellular mechanism

Primary Physiological action(s)

Advantages Disadvantages

action(s)

Biguanides Metformin Activates AMP-kinase

Hepatic Glucose Production

Extensive ExperienceNo weight gainNo hypoglycemiaLikely CVD Events

Gastrointestinal side effectsLactic acidosis risk (rare)Vitamin B12 d fi ideficiencyMultiple contraindications: CKD, acidosis, hypoxia, dehydration etc.

Sulfonylureas Glibenclamide / glyburideGlipizideGliclazideGlimepiride

Closes KATP channels on beta cell plasme membranes

Insulin secretion Extensive experienceMicrovascular Risk (UKPDS)

HypoglycemiaWeight gainBlunts myocardial ischaemic preconditioning ?Low durability

Meglitinides RepaglinideNateglinide

Closes KATP channels on beta cell plasme membranes

Insulin secretion Postprandial glucose excursions Dosing flexibility

HypoglycemiaWeight gainBlunts myocardial ischaemic preconditioning ?Frequent dosing

h d lschedule


Properties of available glucose-lowering agents that may id t t t h i i T 2 Di b t tguide treatment choice in Type 2 Diabetes cont.




( )

Thiazolidinediones

PioglitazoneRosiglitazone

Activates the nuclear transcription factor PPAR-y

Insulin Sensitivity No hypoglycemiaDurabilityHDL-C Triacylglycerols (pioglitazone)CVD Events ?

Weight GainOedema / Heart FailureBone FracturesLDL-C (rosiglitazone)CVD Events ? (rosiglitazone)Mn (meta-analyses, rosiglitazone)Bladder Cancer ? (pioglitazone)

a-Glucosidase Acarbose Inhibits Slows intestinal No hypoglycemia Modest HbA1ca-Glucosidase Inhibitors

AcarboseMigitolVoglibose

Inhibits intestinal a-glucosidase

Slows intestinal carbohydrate digestions / absorption

No hypoglycemiaPostprandial glucose excursions CVD Events Non-systemic

Modest HbA1c efficacyGastrointestinal side effects (flatulence, diarrhoea)Frequent dosing schedule

DPP-4 Inhibitors

SitagliptinVildagliptinSaxagliptinLinagliptinAlogliptin

Inhibits DPP-4 activity, increasing postprandial active incretin (GLP-1, GIP)

Insulin secretion (glucose-dependent)Glucagon secretion (glucose-dependent)

No hypoglycemiaWell tolerated

Modest HbA1c efficacyUrticardia/Angio-oedemaPancreatitis ?

(GLP 1, GIP) concentrations


Properties of available glucose-lowering agents that id t t t h i i T 2 Di b t tmay guide treatment choice in Type 2 Diabetes cont.




action(s)

GLP-1 Receptor Agents

ExenatideLiraglutide

Activates GLP-1 receptors

Insulin secretion (glucose-dependent)Glucagon secretion (glucose-dependent)Slows gastric emptying

No hypoglycemiaWeight reductionImproved beta cell mass / function ?Cardiovascular

Gastrointestinal side effects (nausea / vomiting)Acute pancreatitis ?C cell hyperplasia / medullary thyroidemptying

Satiety Cardiovascular protective actions ?

medullary thyroid tumoursInjectableTraining Requirements

I li H NPH A i Gl di l U i ll H l iInsulin Human NPHHuman RegularLisproAspartGluisineGlargineDetermir

Activates insulin receptors

Glucose disposal Hepatic glucose production

Universally effectiveTheoretically unlimited efficacyMicrovascular Risk (UKPDS)

HypoglycemiaWeight gainMitogenic effects ?InjectableTraining Requirements‘Stigma’ forDetermir

Pre-mixed (several types)

Risk (UKPDS) Stigma for patients


OAD’s and IncretinsWorkshopWorkshop


•Understand the different classes of OAD’ d h t

•Different start and intensification options for OAD i t d di OAD’s and when to

use which OAD’s –either as monotherapy

i bi ti ith

OADs exist depending on the need for the individual patient

or in combination with other OAD’s / Insulin

•Metformin will generally be the first drug of choice

Group Discussion

LECTURE

Insulin Initiationand Monitoring

Lecture:

Insulin Initiation and Monitoring

30 minutes

The Usage of InsulinLectureLecture


• Understand the insulin mechanism of action and its relationship to blood glucose

• Understand the current usage of Insulin in Indonesia

• Understand the different types of insulin, when to use insulin and the different insulin regimentsthe different insulin regiments

• Understand the relationship between insulin dosage and blood glucose measurements

Treatment therapies for Type 2 diabetesWhen and How to start treatmentWhen and How to start treatment


Basal

Lifestyle + Metformin

+-other OAD or GLP-1 agonists

Basal Insulin

Premix Insulin

Basal + Bolus

Insulin

HbA1c ≥7.0%


Insulin remains the most efficacious glucose l i tlowering agent

Decrease in HbA1c: Potency of monotherapy

HbA

1c%

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

What is InsulinWhat is Insulin

• After a meal carbohydrates are digested and enter the bl d t hi h t tblood system, which transports them to the cells

• Some cells (those ofINSULINis needed

for glucose uptakeand storage

• Some cells (those of muscles and fat tissue) need assistance to have blood sugar enter into them and to b d f d tibe used for energy production

• The liver needs assistance to t t th f t fstart the process of storage of

glucose in the form of glycogen

Insulin secretion is delayed and blunted in Type 2 i bDiabetes

The goal of insulin therapy is to restore normal insulin secretion

‘G ’ h d

Normal

800Meal Meal Meal

‘Gap’ that needs to be covered

Type 2 diabetes600

400Insulin

S ti 400

200

Secretion (pmol/min)

0

Adapted from: Polonsky KS, et al. N Engl J Med. 1996 Mar 21;334(12):777-783.

Time (24 hours)

How Insulin acts in the body

Insulin

Insulin binds to the insulin receptors on the cell membranes of the target cells in the liver, muscles and adipose tissue

Liver Adipose TissueMuscles

• Inhibits glucose production

• Promotes formation

• Promotes uptake and utilization of glucose

• Promotes uptake of glucose

• Suppresses lipolysisof glycogen and its storage

• Suppresses lipolysis

Objectives of Insulin Treatment

Maintain blood glucose levels between 80-140 mg/dl:

1 By promoting uptake of glucose by target cells

j

1. By promoting uptake of glucose by target cells

• subsequent breakdown into energy (glycolysis)

• storage as glycogen (glycogenesis)• storage as glycogen (glycogenesis)

2. By inhibiting new glucose formation from non carbohydrate

source (gluconeogenesis) or production of glucose by liver

3. By suppressing lipolysis (breakdown of fat)

Most people with type 2 diabetes will, in time, need insulin therapy becauseneed insulin therapy because…

)60

requ

iring

ns

ulin

(%)

30

40

50

Pat

ient

s r

addi

tiona

l i

10

20

30

Years from start of UKPDS

a

0

10

1 2 3 4 5 6

Wright A et al. Diabetes Care 2002;25:330–6

(Patients treated with chlorpropramide) Years from start of UKPDS

…diabetes Patients will eventually fail on OAD’s

UKPDS9

Conventional*GlibenclamideMetforminInsulin 8

ADOPTMetforminGlibenclamide

Rosiglitazone

A1

c(%

)

8

Insulin8.5

8

7.5

Med

ian

Hb

A

7

7.5

6 5

Recommended treatment

target <7 0%†

7

6.5

6.2% – upper limit of normal range6

Years from randomisation2 4 6 8 100

6.5 target <7.0%†

6

i ( )0 2 3 4 51

Years from randomisation Time (years)

*Diet initially then sulphonylureas, insulin and/or metformin if FPG>15 mmol/L; †ADA clinical practice recommendations. UKPDS 34, n=1704

UKPDS 34. Lancet 1998:352:854–65; Kahn et al (ADOPT). NEJM 2006;355(23):2427–43

Insulin can be initiated at any time…Insulin can be initiated at any time…

• Traditionally, insulin has been reserved as the last line of therapy…

• …However, considering the benefits of normal glycemic status, Insulin can be initiated earlier and as soon as possible

Inadequate Lifestyle + 1 OAD + 2 OAD + 3 OAD

INITIATE INSULIN

…but Insulin usage is currently very low in I d i d t it i hb i t i

Population Total Insulin Used Insulin Usage per Capita

Indonesia compared to its neighbouring countries

Bangladesh 161

Indonesia 248

3,097

694

19

3

Philippines 104 982 9

67

92

Thailand

Vietnam

3,258

417

49

5

29Malaysia

Million People Mega Units

2,029 70

Insulin Units / Capita

IMS Full year 2011 Data. CIA World Factbook

Million People Mega Units Insulin Units / Capita

Insulin Indications

Absolut Indication

Type 1 Diabetes

Relative IndicationRelative Indication

Patients who fail to reach target with OAD optimal dosage

(3-6 months)

Type 2 DM Outpatient with:

Pregnancy not controlled with diet

Infected Diabetes Feet

High Blood Glucose Fluctuations

Repeated History of Ketoacidosis

History of PankreotomiHistory of Pankreotomi

Besides the above, there are a number of condition where insulin is

required, e.g. chronic liver, kidney function interruption and high

dosage steroid therapy

Three Types of InsulinSchematic Representation OnlySchematic Representation Only

BASAL INSULIN

min

)

BASAL INSULIN

PRE-MIX INSULIN

FAST-ACTING INSULIN

R (

mg

/kg

/m

GI

Time (h)

0 4 8 12 16 20 24

Three Types of Insulin

FAST-ACTINGPRE-MIXBASALm

in)

min

)

min

)

GIR

(m

g/k

g/m

GIR

(m

g/k

g/m

GIR

(m

g/k

g/m

Time (h)

G

0 8 16 20 244 12Time (h)

G

0 8 16 20 244 12Time (h)

G

0 8 16 20 244 12

Basal Insulin provides a steady concentration of

insulin in the bloodstream

Premixed insulins contain a mixture of rapid-acting and intermediate-acting

Fast-acting insulinsinclude single amino acid replacement that reduce

their ability to self-over 24 hours. Initially, basal insulin should be

given at 10 units per day at night time or in the

morning1

ginsulin in a fixed

combination to provide coverage of prandial and

basal insulin requirements2

yassociate into diamers and

hexamers. This means that they are quickly

absorbed into the bloodstream following

1. Hompesch M. Diabetes Obes Metab 2006; 8:568; 2. Weyer et al. Diabetes Care 1997;10:1612–1614.; 3. 1. Heinemann et al. Diabetes Care. 1998;21:1910–4

morning1 requirements2 bloodstream, following subcutaneous injection.3

Pharmacokinetics of the different Types of Insulin available in Indonesia

Profile

Type of Insulin Insulin Name Onset (hours)

Peak (hours)

Fast-acting Analogue Insulin Insulin Aspart (NovoRapid) 0.2 – 0.5 0.5 - 2

Insulin Lispro (HumaLog) 0.2 – 0.5 0.5 - 2

Insulin Gluisine (Apidra) 0.2 – 0.5 0.5 - 2

Fast-acting Human Insulin ActRapid 0.5 – 1 0.5 - 1

Humulin R 0.5 – 1 0.5 - 1

Intermediate Human Insulin Insulatard 1.5 – 4 4 - 10

Humulin N 1.5 – 4 4 - 10

Long-acting Analogue Insulin Insulin Detemir (Levemir) 1 - 3

Insulin Glargine (Lantus) 1 - 3Insulin Glargine (Lantus) 1 3

Pre-mix Analogue Insulin Insulin Aspart (NovoMix) 0.2 – 0.5 1 - 4

Insulin NPL (HumaLog) 0.2 – 0.5 1 - 4

Pre-mix Human Insulin Mixtard 0 5 – 1 3 - 12Pre mix Human Insulin Mixtard 0.5 1 3 12

Humulin Mix 0.5 – 1 3 - 12

Adapted from Mooradian et al. Ann Intern Med 2006; 145: 125-34

Basic Insulin Start Recommendation

If Fasting Blood Glucose is elevated • Start with Basal Insulin

If both Fasting and Prandial Blood Glucose are elevated

• Start with Premix Insulin• OR add Basal Insulin to OAD

Glucose are elevated • OR Start Basal/Bolus Therapy

Source: ADA Guidelines

Insulin Titration schemesB l d F t A ti I liBasal and Fast-Acting Insulin

Fasting Blood Glucose Content (mg/dl) Basal Insulin TitrationContent (mg/dl)

<70 mg/dl Reduce dosage with 2 units

70-130 mg/dl Maintain dosage

130-180 mg/dl Increase dosage 2 units per 3 days

BASAL INSULIN

>180 mg/dl Increase dosage 4 units per 3 days

Once titrated, continue to monitor HbA1c every 3 months

Fasting Blood Glucose Content (mg/dl) Fast-acting Insulin Titration

Start with 4 units / day Increase by 2 units every 3 days FAST-

ACTING Start with 4 units / day until target is reached

When starting Fast-acting Insulin, secretagogues should be discontinued

ACTING INSULIN

Source: KONSENSUS: Insulin Treatment 2011

Insulin Treatment OptimizationH t O ti i T t t ft I iti tiHow to Optimize Treatment after Initiation

Basal Insulin OnlyUsually with OAD

Start with Basal Insulin 10u / daily with meal Usually with OAD10u / daily with meal or before bedtime. Same injection time every day

If glycemic target is not reached titrate according to Basal Titration Scheme

If glycemic target is not reached within 2-3 months,

Basal Insulin OnlyUsually with OAD

,intensify Insulin treatment

Basal with Prandial

Usually keep OAD

Premix InsulinUsually keep OAD

Basal BolusUsually keep OADUsually keep OADy p y p

Add Prandial starting with 4u / day either

once or twice-daily and

Switch to Premix twice-daily. Start with equal basal dose, but give 50% per injection

Switch to Basal Bolus (3 daily prandial) start

with 4u / day andonce or twice daily and titrate accordingly

but give 50% per injection and titrate accordingly

with 4u / day and titrate accordingly)

Source: PERKENI Insulin Guidelines 2011

Primarily one type of Insulin device available in Indonesiay yp

Prefilled devices

• Disposable – disposed of once empty

• Less teaching time required

• Primarily plastic

• Easy and Convenient for Patients

WE WILL COVER HOW TO START A PATIENT ON INSULIN AND

INJECTION TECHNIQUES IN AINJECTION TECHNIQUES IN A SEPARATE WORKSHOP

WE WILL COVER HOW TO START A PATIENT ON INSULIN AND INJECTION TECHNIQUES IN A SEPARATE GROUP

DISCUSSION

LECTURE

Screening, Treatmentand Evaluation of

Complications

Lecture:Screening, Treatment and Evaluation

of Complications

Screening, Treatment and Evaluation of C li tiComplicationsLecture


• Understand the treatment options for diabetes associated lcomplications:

• Nephropathy

• Retinopathy• Retinopathy

• Neuropathy

• Erectile Dysfunction• Erectile Dysfunction

• CVD

• CAD

Recap: The goal of diabetes management is to secure optimal glycemic control to avoid complicationsoptimal glycemic control to avoid complications

Di b tiStroke

Microvascular Macrovascular

DiabeticretinopathyLeading causeof blindness

1.2- to 1.8-fold increase in stroke3

in working-ageadults1

Diabetic75% diabetic patientsDiabetic

nephropathyLeading cause of end-stage renal

Diabeticneuropathy

patients die from CV events4

renal disease2

eu opat yLeading cause of non-traumatic lower extremity amputations5

Erectile DysfunctionThe most secretive

amputations5

1Fong DS, et al. Diabetes Care 2003;e 26 (Suppl.1):S99–S102. 2Molitch ME, et al. Diabetes Care 2003; 26 (Suppl.1):S94–S98. 3Kannel WB, et al. Am Heart J 1990; 120:672–676. 4Gray RP & Yudkin JS. Textbook of Diabetes 1997. 5Mayfield JA, et al. Diabetes Care 2003; 26 (Suppl.1):S78–S79.

Diabetic FootComplication of DM

Recap: Risk of Complications increases as Hb1Ac increasesHb1Ac increases

80

0

40

60

M di l i f ti

Microvascular disease

e per

1.0

00

nt-

year

s

20

40 Myocardial infarction

Inci

den

cepat

ien

05 6 7 8 9 10 11

Updated Mean HbA1c (%)

Stratton IM et al. BMJ 2000;321:405–12

Updated Mean HbA1c (%)

Adjusted for age, sex, and ethnic group

Recap: It’s the diabetes-related complications – not the diabetes medicine - that carries the biggest cost ggto the society

Cost increases with a factor of 22.5 if patients develop complications (ASKES Data)

900

700

800

900US$

400

500

600

700

22.5X

40100

200

300

400

400

With ComplicationsWithout Complications

Approximate Annual Cost / Diabetes Patient

ASKES 2010 Unpublished data

Positive legacy effect of earlier glucose control

Provides long-term reductions in both microvascular and macrovascular complications

15%p=0 01

24%p=0 001

13%p=0 007

9%p=0 04

16%p=0 052

25%p=0.0099

6%p=0.44

12%p=0 03

RRR* at end of UKPDSRRR* at end F/U (median 8.5 years)

p=0.01 p=0.001 p=0.007 p=0.04p=0.052 p=0.0099 p=0.44 p=0.03

Any diabetesendpoint

Microvascular

Myocardial infarction

Death (any

cause)Microvascular

disease

RRR: relative risk reduction of intensive therapy over conventional therapy

UKPDS 80. Holman et al. NEJM 2008; 359:1577-89.

Classification of Micro- and MacrovascularC li tiComplications

Chronic complications of diabetes

• Microvascular complications• Kidney – nephropathy » kidney failure• Eyes – retinopathy » blindness• Eyes – retinopathy » blindness• Nerves – neuropathy » disability• Peripheral Arterial Diseases » disability• Erectile Dysfunctiony

• Macrovascular complications• Heart – myocardial infarction• Brain – stroke• Atherosclerosis – myocardial infarction

Microvascular Complications – an overviewMicrovascular Complications an overview

Retinopathy and blindnessp y

NephropathyNephropathy

Erectile Dysfunction

Neuropathy

Erectile Dysfunction

International Diabetes Federation. Diabetes Atlas 2006;111–2

Diabetes NephropathyCh t i tiCharacteristics

• Persistent albuminuria

• Diabetic retinopathy

• H pe tension• Hypertension

• Decline in kidney function (about 12 ml/min/year)

Assessment of Kidney function in Diabetes Mellitus type 2

GUIDELINES

A.Annual Screening for albuminuria by : Albumin Excretion Rate (AER) – timed urine collection

AER

mg/ hour ug/min *in timed collectionMicroalbuminuria 30 - 300 20 - 200Macroalbuminuria >300 >200

OR Albumin : Creatinine Ratio (ACR) – spot urine sample

ACR Males (mg/mmol) Females (mg/mmol)

Microalbuminuria 2,5 - 25 3,5 - 35Macroalbuminuria >25 >35

If AER or ACR screening is positive for microalbuminuria : Perform additional ACR or AER measurements one to two times within 3 months.

Microalbuminuria is confirmed if at least two or three tests (including the screening test) are positive.

If AER or ACR screening is positive for macroalbuminuria : Perform a 24 h urine collection for quantitation of protein excretion. AND

B. Annual estimation of the Glomerular Filtration Rate (eGFR) eGFR Indicates

<60 mL/min per 1,73 m2 At least moderate kidney dysfunction (stage 3 – 5 chronic kidney disease (CKD))

60 – 90 mL/min per 1,73 m2 Mild kidney dysfunction (stage 2 CKD if albuminuria also present)

Continue annual screening for albuminuria and eGFR in the event of negative screening tests.

Reference : Chadban, et al. Nephrology 2010; 15, S146-S161

Natural history of diabetic nephropathy

Urinary protein excretionGFR

mg

/d

)

GFR

) Incipient diabeticnephropathy

Pre Overt diabeticnephropathy

End-stagerenal disease

excr

eti

on

(m

ati

on

rate

(G

/m

in)

150

100 1000

50001 2 3 4 5

ary

pro

tein

e

meru

lar

filt

ra(m

L/ 100

50200

1000

Uri

na

Years

Glo

m

05 10 15 20 25

20

FunctionalGFR -

(90-95%)Microalbuminuria,

hypertensionProteinuria, nephrotic

syndrome, GFR ¯

.Vora JP, et al. In: Johnson RJ, Feehally J, eds. Comprehensive Clinical Nephrology. New York: Mosby; 2000

Treating AlbuminuriaTreating Albuminuria

• Use ACE-I or ARB in nonpregnant patiens with micro-or macroalbuminuria

• Reduce protein intake to 0.8-10 g/kgBW/day in DM & early CKD; 0.8 g/kgBW/day in later CKD

• If ACE-Is /ARBs/diuretics are given, monitor serumIf ACE Is /ARBs/diuretics are given, monitor serum creatinine and potassium

• When eGFR <60 ml/min/1.73m2, evaluate for CKD complicationscomplications

• Consider referral to experienced physician in kidney disease care

Diabetes Care. 2012

Diabetes NephropathyP ti d T t tPrevention and Treatment

• Maintain tight glycaemic and blood pressure controland blood pressure control

• Multifactorial disease management:

0 4

0.8

0.6

ty o

f m

inuria

management:• antihypertensive agents• good blood glucose control• control of dyslipidaemia

0.0

0.4

0.2

Probab

ilim

icro

album • control of dyslipidaemia

• monitoring renal function• lifestyle changes, including

smoking cessation and

Glycated haemoglobin (%)

5 8 12111096 7smoking cessation and low-protein diet

DCCT. Diabetes 1996;45:1289–98

Diabetes RetinopathyRi k F t d Cl ifi tiRisk Factors and Classification

• Poor glycaemic and blood pressure controlti

o) 35

blood pressure control increase the risk of retinopathy

• Five categories:ce (

odds

ra 30

25

20 • Five categories:• background

• preproliferative

lif tithy

inci

den

c

10

15

• proliferative

• advanced diabetic eye disease

mac lopathLondon HbA (%)

Ret

inopat

4 6 9

0

5

875 10

• maculopathyLondon HbA1c (%)

DCCT HbA1c (%)

5.7 7.7 10.89.88.86.7 11.9

Chaturvedi et al. Diabetes Care 2001;24:284–9

Diabetes Retinopathy

Non-Diabetic RetinaRetina

Diabetic Maculopathy

Proliferative Diabetic Retinopathy

Diabetes RetinopathyP ti d T t tPrevention and Treatment

• Maintain tight glycaemic and blood pressure control• Maintain tight glycaemic and blood pressure control• Regular eye examinations• Treat with laser photocoagulation and vitreoretinal

surgery

Klein et al. Ann Intern Med 1996;124:90–6

Diabetes NeuropathyRi k F t d C TRisk Factors and Common Types

• Hyperglycaemia Symmetrical

diffuse sensorimotor

Femoral neuropathy Other acute

mononeuropathies Pressure palsies

is the leading cause of diabetic neuropathy

sensorimotor neuropathy (amyotrophy) mononeuropathies

VIIII

Truncal

Ul • Alcohol makes neuropathy worse

• A number of

Ulnar

MedianLateral

lit lclinical syndromes are recognisable

Sensory loss 0 → +++

Pain + → +++

Tendon reflexes N → ↓

Sensory loss 0 → +

Pain + → +++

Tendon reflexes ↓ → 0

Sensory loss 0 → +

Pain + → +++

Tendon reflexes N

Sensory loss + → +++

Pain + → ++

Tendon reflexes N

popliteal

Watkins et al. In: Diabetes and Its Management 2003. Pickup & Williams. In: Slide

Pickup & Williams. In: Slide Atlas of Diabetes 2004

↓

Motor deficit 0 → +

↓

Motor deficit + → +++ Motor deficit + → +++ Motor deficit + → +++

Watkins et al. In: Diabetes and Its Management 2003. Pickup & Williams. In: Slide Atlas of Diabetes 2004

Diabetes NeuropathyThe Most Frequent Diabetes related Complication inThe Most Frequent Diabetes related Complication in Indonesia (and in the World…)

A1Chieve Indonesia (2.240 patients)

IDMPS Indonesia (715 patients)

80%

90%

100%

( p )

80%

90%

100%

( p )

41.9%40%

50%

60%

70%

54.0%

40%

50%

60%

70%

6.7%16.1%19.1%21.7%

10%

20%

30%

40%

8.7%

26.5%33.4%

10%

20%

30%

40%

0%Neuropathy EyeCV Renal Foot

UlcerFrequency of complications

0%Neuropathy Eye Renal Foot

UlcerFrequency of complications

Note: One patient can have more than one complication

Diabetes NeuropathyP ti d T t tPrevention and Treatment

• Maintain tight glycaemic t l t d th16 control to reduce the

risk or progression of neuropathy

• Exclude or treat

16

affe

cted

p<0 00112

Conventional therapy

• Exclude or treat contributory factors:• alcohol excess• vitamin B12

8

ge

of ca

ses p<0.001

vitamin B12deficiency

• uraemia• Offer pain relief based Pe

rcen

tag

4Intensified therapy

O e pa e e basedon the dominant symptoms

00 1

Time (years)2 3 4 5

DCCT. NEJM 1993;329:977–86

Diabetic Foot ComplicationsDiabetic Foot Complications

Erectile DysfunctionD fi itiDefinition

ED is the inability to achieve and maintain an erection adequate for intercourse to the mutual satisfaction ofadequate for intercourse to the mutual satisfaction of the man and his partner.

Remember both partners in a relationship are affectedRemember, both partners in a relationship are affected

Erectile DysfunctionB k dBackground

• 35%-75% of men with diabetes will experience at least some degree of EDsome degree of ED

• Men with diabetes tend to develop erectile dysfunction 10 to 15 years earlier than men without diabetes. o 5 yea s ea e a e ou d a e es

• Men with diabetes will have ED• 50%-60% in > 50 years old50% 60% in > 50 years old• 95% in >70 years old

Erectile DysfunctionRi k F tRisk Factors

Risk Factors

Neuropathy

Peripheral vascular disease

Poor glycemic control

Diabetes duration and complications

Age and high BMI

Smoking doubles the risk

Erectile DysfunctioniTreatment Options

• Oral medications: Sildenafil (Viagra), Vardenafil (Levitra),

Tadalafil (Cialis)Tadalafil (Cialis)

• Urethral suppositories (MUSE)

• Injection therapy: Caverject Trimix Bimix• Injection therapy: Caverject, Trimix, Bimix

• Vacuum constriction device

• SurgerySurgery

• Sex therapy

Macrovascular Complications – an overviewp

Stroke

Cardiovascular/heart disease

Peripheral vascular disease

Cardiovascular DiseasesP ti t ith T 2 Di b t t i d i k f CVDPatients with Type 2 Diabetes at a increased risk of CVD

• Risk of cardiovascular disease is greater in

Incidence of myocardial infarction over 7 years disease is greater in

patients with diabetes than in those without

• Having diabetes results in

y

%) • Having diabetes results in

a similar risk of heart attack as a prior heart attackPa

tien

ts (

%

attack

With diabetes n=1059

Without diabetes n=1373

P

Haffner et al. N Engl J Med 1998;339:229–34

Poor Control of CV Risk Factors in Diabetes ( )(NHANES)

Frequency

S Cholesterol < 200 mg/dl (5 2 mmol/l) 52 %• S-Cholesterol < 200 mg/dl (5.2 mmol/l) 52 %

• BP < 130/80 mmHg 36 %

• HbA1c < 7.0% 37 %

• All three risk factors controlled 7 %

• Unchanged CV risk factors from 1991 to 2000

Saydak SH et al. JAMA 2004

g

Cardiovascular DiseasesRisk for Myocardial infaction and stroke increases withRisk for Myocardial infaction and stroke increases with progression to Type 2 Diabetes

Relative risk for MI and stroke in women

kRel

ativ

e risk

R

*Nurses’ Health Study (NHS) cohort comprised women only

No diabetes during study

Prior to diagnosis

After diagnosis

Diabetic at baseline

Adapted from Hu et al. Diabetes Care 2002; 25:1129-34

Prevention of Cardiovascular DiseasesPrevention of Cardiovascular Diseases

• Reduce risk factors for d l d

ears

Non-diabetic subjects

140

cardiovascular disease:• stop smoking• treat hypertension

000 p

atie

nt-

y Subjects with type 2 diabetes

100

120

• treat hyperlipidaemia• improve glycaemic

controld i ht i th

aths

per

10,0

60

80

• reduce weight in the obese

• take regular exercise

Num

ber

of

dea

20

40

Number of risk factors

N

0 1 2 30

Adapted from Stamler et al. Diabetes Care 1993;16:434–44

Treatment of Cardiovascular Diseases Risk factors

• Hypertension• Dyslipidemia


Dyslipidemia• Antiplatelet agents• Smoking cessation

CHD screening and treatment• CHD screening and treatment

Diabetes Care 2012


Hypertension SBP ≥140 or DBP ≥90 mmHg:Hypertension SBP ≥140 or DBP ≥90 mmHg:Lifestyle modification +pharmacological therapy

Dyslipidemia Lifestyle modification + statinsDyslipidemia Lifestyle modification + statins

Antiplatelet agents Aspirin and/or clopidogrel

Smoking cessation Stop smoking, counseling

CHD screening and treatment

ACE-I and aspirin and statin (if not contraindicated)treatment contraindicated)

Diabetes Care 2012

HypertensionHypertension

• SBP 130-139 or DPB 80-89 mmHg: lifestyle modification (DASH) for 3 months, if fails pharmacological agents

• SBP ≥140 or DBP ≥90 mmHg lifestyle mod + pharmacological therapypharmacological therapy

• Administer one or more anti-HT meds at bedtime• Monitor kidney function and serum potassium in pt

i i ACE I ARB di tireceiving ACE-Is, ARBs, or diuretics• Remember: ACE-Is and ARBs are contraindicated in

pregnancy

Diabetes Care 2012

Meta-analysis of Statin Treatment in DiabetesMeta analysis of Statin Treatment in Diabetes

Risk reduction of clinical outcomes per 40 mg/dL (1.0 mmol/L) reduction in LDL cholesterol

• 21% reduction major vascular events• 25% reduction in coronary revascularisation• 21% reduction in stroke• 21% reduction in stroke

• 9% reduction in all-cause mortality • 13% reduction in CVD mortality• 13% reduction in CVD mortality• No difference in non-vascular mortality


Lancet 371, 117-25. 2008


Statin Conclusion

• Statin therapy should be considered for all individuals with type 2 diabetesyp

• independent of baseline lipid levels

• However – lack of data for age < 40yg y

• and should be considered for individuals with type 1 diabetes at high risk of CVD or with signs of di b i li idiabetic complications

The STENO2 Study – “a multifactorial approach i b ”to Type 2 Diabetes”

• 160 patients

• Type 2 diabetes and• Type 2 diabetes and microalbuminuria• Mean age 55 yrs, BMI 30

kg/m2; HbA1c 8.4 %

New Engl J Med 2003; 383-93

• Randomized to• conventional therapy

assigned to their GPs

i t i t St• or intensive care at Steno Diabetes Center

New Engl J Med 2008; 358: 580-91New Engl J Med 2008; 358: 580 91

The STENO2 Study – Study DesignThe STENO2 Study Study Design

Conventional treatment

80

Endpoint examinations

Micro-vascular Macro-vascular80

n=160

Intensive treatment

4 years 8 years80

Advice to the Intensive Groupp

• Food Advice• Cut down on animal fatCut down on animal fat• Have some kind of seafood every day

• 5-6 vegetables and fruits every day

• Exercise Advice• Exercise Advice• Enjoy physical performance

> 150 min/week

• Smoking cessation• Smoking cessation • Intensification of OHA and insulin• Treatment with ACE/ARB, Statin and / ,

baby aspirin

Patients in the Intensive Group had obtained better h i i h i loutcomes than patients in the Conventional Group…

Intervention n=55

Standard n=38n=55 n=38

Haemoglobin A1c (%) 7.7 8.0

F-s-total-cholesterol (mg/dl) 147 155F s totalcholesterol (mg/dl) 147 155

F-s-LDL-cholesterol (mg/dl) 71 77

F-s-triglycerides (mg/dl) 99 148g y ( g/ )

Systolic BP (mm Hg) 140 146

Diastolic BP (mm Hg) 74 73

Albumin excretion rate (mg/24h)* 69 75

Values are mean

* median

…and Mortality Rate was lower in the Intensive Group…y p

90

100

60

70

80

20

30

40

50

0

10

20

30% of patients (n=24) died in the intensive group compared to30% of patients (n=24) died in the intensive group compared to 50% of patients (n=40) in the conventional group

Absolute risk reduction = 20%

The STENO2 StudyRi k R d ti i I t i GRisk Reduction in Intensive Group

Relative risk reduction after 8 years

• Cardiovascular disease 53%

• Diabetic Nephropathy 61%

• Diabetic Retinopathy 58%p y

• Autonomic Neuropathy 63%

Screening, Treatment and Evaluation of ComplicationsLectureLecture


• Complications should be screened for and treated according to guidelines

R ti f ll t t t

• Understand the treatment options for diabetes associated complications:

• Routine follow up on treatment of complications should be performed

• CVD complications are the mail

• Nephropathy

• Retinopathy

• NeuropathyCVD complications are the mail cause of death among patients with diabetes

• Risk of end-stage renal disease f

• Neuropathy

• Erectile Dysfunction

• CVD and blindness is significantly reduced by treatment of hyperglycemia and hypertension

• CAD

LECTURE

Simple DiabetesFoot Care

Simple Diabetes Foot Care

Lecture:

30 minutes

Simple Diabetes Foot CareLecture


Understand the risk factors for diabetic• Understand the risk factors for diabetic foot complications

• Understand the steps for a simple diabetes foot examination

• Understand the management of foot ulcers

Why foot care is important to diabetes management

Diabetes Patients

Have 15 – 40 fold higher risk of leg amputation than non

Have a 15 % life time risk of developing foot ulcer

Every 30 seconds a lower limb lost caused by diabetes

5-year suvival rate after major amputation < 50 %than non

diabetic diabetes < 50 %

•85% of diabetes-related amputations are happening in patients with foot ulcers

•Early detection can prevent 40-85 % lower limb amputation

Frykberg et al. J Foot Ankle Surg, 2000. IDF, International Working Group on Diabetic Foot 2007

5 Cornerstones of diabetes foot care management

1. Foot examinationregularlyregularly

2. Identification of risk factors

4. Treatment beforeUlcer occurs

3. Education (patients, providers

and family)5. Use appropriate

footwearand family) footwear

Risk Factors for diabetic foot ulceration

Intrinsic Factors Extrinsic Factors

• Peripheral Neuropathy

• Micro- and Macrovascular Diseases

• Immunopahty

• Minor mechanical trauma

• Callus

• Thermal Injuryu opa y

• Structural Deformity

• Limited Joint Mobility

• Nephropathy

e a ju y

• Chemical Burns

• Bathroom Surgery

• Smoking• Nephropathy

• Age

• Duration of Diabetes

Visual Acuity

• Smoking

• Poor knowledge of diabetes

• Psychological Factors

• Visual Acuity

• Previous Ulceration

Frykberg, Diabetic Microvascular Complications Today, May/June 2006

Pathway to diabetic foot ulceration

90%

100%

63%

77%78%

50%

60%

70%

80%

30%35%37%

20%

30%

40%

50%

1%0%

10%

Peripheral Neuropathy

Peripheral Ischemia

EdemaDeformityMinor Trauma

Callus InfectionsNeuropathy IschemiaTrauma

Components leading to foot ulceration

Reiber GE, Vileikyte, Boyko EJ et al. Causal pathways for incident lower–extremity ulcers in patients with from two settings. Diabetes Care 1999: 157-162

Peripheral Neuropathy Intrinsic Factors

Autonomic SensoricMotoric

Decreased Sweating

Dry Skin

• Loss of protective

sensation

• Decreased pain

Decreased Elasticity

Fissure / Callus

p

threshold

• Lack of temperature

sensation and Fissure / Callus

Ulcer

proprioception

Th l T Ill fittiThermal Trauma in ‘bajaj’

Ill fitting Shoes

Neuropathic Ulcers Intrinsic Factors

Influenced by:

- Friction

- Pressure

Peripheral Arterial Disease (PAD)Intrinsic Factors

Risk Factors* PAD

• Hyperglycemia

• Eleveted systolic blood

pressure

• Correlated with atherosclerosis

• A1c 1% 26 % PAD

• More aggressivepressure

• hyperlipidemia

• Smoking

• Cardiovascular disease

• More aggressive

• Narrowing vessel lumen …

obstructive

• Distal tissue necrosis• Cardiovascular disease • Distal tissue necrosis

* UKPDS

Foot Deformities / Biomechanical

Intrinsic Factors

Causes of Ulcers (Extrinsic Factors)Kyoto Foot Meeting 2010Kyoto Foot Meeting 2010

Extrinsic Factors

Pathophysiology of diabetic foot

Di b t M llitDiabetes Mellitus

Neuropathy Trauma Vascular Disease

MOTOR

Weakness Atrophy

AUTONOMICSENSORY

Anhidrosis dry skin

MICROVASCULAR MACROVASCULAR

Structural capillary BM

Structural atherosclerosis

High Plantar

Deformity

Abnormal Stress

Loss of Protective Sensation

skin capillary BM thickening

Functional AV

atherosclerosis

Occlusive narrowing

High Plantar Pressure

Callus Formation

Sympathetic Tone

Shunting Ischemia

Structural Deformity

Cheiroarthropathy

Impaired Response to Infection

Ischemia

Diabetic Foot Ulcer AmputationAmputation

Diabetic Foot Disorders: A Clinical Practice Guideline (2006 Revision)

From Theory to real-life – studies on foot care in RSCM

RSCM 2003 RSCM 2007

32%

16% 14%

26%

50%

26%

36%

DiedMajor Amputation and then ImprovedDischarge on their own will

DiedAmputationNo Amputationg

Improved without amputation

Clinical Classification of diabetic foot (Edmond)

Grade 1Grade 1 Grade 2Grade 2 Grade 3Grade 3 Grade 4Grade 4 Grade 5Grade 5 Grade 6Grade 6

Normal foot, no risk factors of neuropathy

No active ulcers, have ≥1

risk factors

Skin breakdown;

fisurre blitser

Foot develop infections,Discharge

Tissue necrosis with or with out intake

Unsalvageable foot, need

majorof neuropathy, ischemia,

deformities

risk factors: neuropathy,

ischemia, deformities, callus and

fisurre, blitser, ulcer

Usually in plantar surface

Discharge purulent, cellulitis,

neuropathy and or

out intake foot,

neuropathy, ischemia,

neuroischemi

major amputation,

extensive necrosis,

destroyed footcallus and swelling, nail deformities

and or ischemia

neuroischemi, infection

destroyed foot,severe

infection

6 Steps for a complete Diabetes Foot Examination6 Steps for a complete Diabetes Foot Examination

DIABETES FOOT EXAMINATIONDIABETES FOOT EXAMINATION

Patient Gross A Vascular Screening

fDerma-t l i Nail Defor-

History Assess-ment Examinationfor

neuropathy tologic

Examination maties

First 4 steps in the assessment

A t Si ifi t Fi diAssessment Significant Finding

Patient History

- Previous foot ulceration- Previous amputation - Diabetic > 10 years

A1 7 %- A1c > 7 %- Impaired vision- Neuropatic symptoms- Claudicatio

Gross Hammer toesGross Inspection

- Hammer toes- Claw toes- Halux valgus - Corn, callus, callus with ulcer, bunion- Prominent metatarsal head

Dermatologic Examination

- Dry skin- Absence of hair- Yellow or erythematous scale- Ulcer or healed ulcer - Interspace maseration- Moist - Uhealing ulceration

N il Y ll thi k d ilNail Deformaties

- Yellow, thickened nail- Ingrowing nail edge- Long or sharp nails

Last 2 steps in the assessment

Assessment Test Significant Finding

Screening for Neuropathy

- Semmes-Weinstein monofilamen 10 gram

Lack of perseption at one or more side

- Tuning fork 128Hz Negative of vibration perception

- Biothesiometer: Vibration perseption

Vibration perseptionthreshold >25 volt

Vascular - Palpation of dorsalis • Decrease or absent Examination

ppedis and tibialisposterior arteri

- Ankle Brachial Index- Color doppler

pulse• ABI < 0.9 consistent

with PAD

ABI>1.2

0.9 – 1.20 9

InterpretationRigid or calcified vessels or bothNormal (or calcified)I h i<0.9

<0.6IschaemiaSevere ischaemia

Risk Classification based on Foot Assessment

Score Category Risk Profile Check-up Frequency

0 Low Risk • Pulsation ADP and ATP good Once a year

• No deformities (hammer toe, claw toes, halux valgus, prominent methatarsal head)

1 Increased Risk • Pulsation ADP and ATP good Once every g

• And/or deformities (hammer toe, claw toes, halux valgus, prominent methatarsal head)

y6 months

2 High Risk • ABI < 0,9 or ADP/ ATP not palpable

• Deformities ( hammer toe, claw toes, halux valgus, , prominent methatarsalhead

Once every 3 months

head

3 Very High Risk • History of ulcer or amputation

• Ulcer

Once every 1-3 months

Intervention based on Risk Classification

Score Category Intervention

0 Low Risk

• Encourage extended knowledge on diabetes and foot care0 Low Risk

• Encourage self-care

1 Increased Risk

• Inspect patient’s feet• Review need for vascular assessment

1 Increased Risk• Evaluate footwear• Enhance foot care education

• Inspect patient's feet• Review need for vascular assessment

2 High Risk

Review need for vascular assessment• Evaluate provision and provide appropriate• Intensified foot care education• Specialist footwear and insoles

Ski d il• Skin and nail

3 Very High Risk

• Multidisciplinary foot care team : • They should have unhindered access to suites for

managing major wounds,• Urgent inpatient facilities• Antibiotic administration

Prevention of Diabetes Foot

DOCheck your feet everyday

DON’T’sWalk without shoes

Always wear footwear

Check your footwear before wearing them

U h th t fit

Use shoes that don’t fit

Use socks that don’t fit to your foot

L t ki b dUse shoes that fit

Buy shoes in the afternoon

Always use socks of cotton

Let your skin become dry

Use sharp items to remove warts

Smoke

Wash your shoes with soft soap and dry them

Cut your nails in a flat way

Use ring on finger

Use high heels or shoes with sharp edges

Check your feet regularly at thedoctor

Use lotion regularly at your skin

p g

Management of Foot Ulcers

Metabolic Control

2

Control

1 3

Infection Control

Wound Control

Vascular Control

Mechanic Control

4

5

International Working Group on the Diabetic Foot 2007

Wound Control1

1 Insision drainage1. Insision, drainage, debridemant and necrotomi

2 Management of2. Management of infections in tissue and bone

3. Exudat Managementg

4. Keep control of proliferation phase and infections

Metabolic Control2

1. Hyperglycemia

- Will inhibit process of wound recovery

- Inhibit growth factor, collagen synthesis and fibroblast activities

2. Hyperalbuminemi

3. Hypertension

4. Decrease of heart and kidney function4. Decrease of heart and kidney function

5. Dyslipidemia

6. Anemia

7. Other diseases caused by diabetes

Infection Control3

1 Need aggressive therapy1. Need aggressive therapy

2. Usually there are no symptoms or signs of infection

3 E t l I f ti P iti3. External Infection: Positive gram bacteria

4. Internal Infection: Negative gram bacteriagram bacteria

5. Might need surgery

Use of Antibiotics3

Choice of antibiotics should be determined by:

1. Condition of the Infection:

- Stage of infection and history of antibiotics

- Bone infection, condition of blood vessels

2. Type of bacteria

- Anarob, aerob, gram positive / gram negative

3. Condition of the patient

- Allergy, heart and kidney function

4 Drug Profile4. Drug Profile

- Safety, drug interactions, adverse events, frequency and dosage and price

Vascular Control4

1. Neuroischemic Foot1. Neuroischemic Foot

2. Atheroscelrosis can cause total block in the blood vessels

3. Decrease of blood flow to the wound

4. Critical Limb ischemia: Amputation Warning

Mechanic Control5

1. Princip:p

Reduce stress on the wound

• Off loading

• Might be bed rest

• Non-weight bearing

• Use of walker wheel-chair or crutches• Use of walker, wheel-chair or crutches

• Use special shoes (‘half-shoes’)

• Distribute the body weight to all surfaces of the foot

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