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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
Source: KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2
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
Source: KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2
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
Source: KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2
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
Slide 19
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
Main Learning PointsMain Learning Points
• 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
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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
Eat Less of These Eat More of These
Chicken Fish TofuSausages processed meat Chicken, Fish, TofuSausages, processed meat, Shrimps and shell fish, Red Meat
Fat
Eat Less of These Eat More of These
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
Main Learning PointsMain Learning Points
• 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
Main Learning PointsMain Learning Points
• 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
START TREATMENT OAD TREATMENT START INSULIN INSULIN INTENSIFICATION
Lifestyle + Metformin
+-other OAD or GLP-1 agonists
Basal
Basal Insulin
Premix Insulin
Basal + Bolus
Insulinagonists
HbA ≥7 0%
Insulin
HbA1c ≥7.0%
Adapted from Raccah et al. Diabetes Metab Res Rev 2007;23:257.
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
Krentz AJ, Bailey CJ. Drugs 2005;65:385–411.
* 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%
• FPG reduction of 20-60 mg/dl
• 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.
* Efficacy depends on existing blood glucose levels
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,
• FPG reduction of 10-20 mg/dl
• 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.
* Efficacy depends on existing blood glucose levels
, 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*
Krentz AJ, Bailey CJ. Drugs 2005;65:385–411.
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
* Efficacy depends on existing blood glucose levels
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
• PPG reduction of 45-55 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,
* Efficacy depends on existing blood glucose levels
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%
• FPG reduction of 6-12 mg/dl
• Associated with moderate and transient nausea, vomiting and • FPG reduction of 6 12 mg/dl
• PPG reduction of 6-18 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.
* Efficacy depends on existing blood glucose levels
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
Inzucci SE, et al. Diabetologia. 2012
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.
Class Compounds(s) Cellular mechanism
Primary Physiological action(s)
Advantages Disadvantages
( )
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
Inzucci SE, et al. Diabetologia. 2012
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.
Class Compounds(s) Cellular mechanism
Primary Physiological action(s)
Advantages Disadvantages
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
Inzucci SE, et al. Diabetologia. 2012
OAD’s and IncretinsWorkshopWorkshop
Main Learning PointsMain Learning PointsSummarySummary
•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
Main Learning PointsMain Learning Points
• 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
START TREATMENT OAD TREATMENT START INSULIN INSULIN INTENSIFICATION
Basal
Lifestyle + Metformin
+-other OAD or GLP-1 agonists
Basal Insulin
Premix Insulin
Basal + Bolus
Insulin
HbA1c ≥7.0%
Adapted from Raccah et al. Diabetes Metab Res Rev 2007;23:257.
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
Main Learning PointsMain Learning Points
• 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
Treatment of Cardiovascular Diseases Risk factors
Dyslipidemia• Antiplatelet agents• Smoking cessation
CHD screening and treatment• CHD screening and treatment
Diabetes Care 2012
Treatment of Cardiovascular Diseases Risk factors
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
Independent of baseline LDL or prior CVD
Lancet 371, 117-25. 2008
Independent of baseline LDL or prior CVD
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
Main Learning PointsMain Learning PointsSummarySummary
• 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
Main Learning PointsMain Learning Points
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