Pradana Soewondo

Department of Internal Medicine

Faculty of Medicine University of Indonesia-
Cipto Mangunkusumo National Referral Hospital
Jakarta, Indonesia
New PERKENI Guideline for Prevention and
Management of Type 2 Diabetes
and Its Supporting Evidence
Outline of Presentation
! Epidemiology diabetes in Indonesia
! History of PERKENI Guidelines
! Results of DiabCare study
! Screening and diagnosis criteria
! Diabetes management and new drugs
! Algorithm of treatment
! Blood glucose monitoring
! Conclusion
Prevalence of IGT and DM In Indonesia
Known DM Undiagnosed
DM
Total DM IGT
1,5 % 4,2 % 5,7 % 10,2 %
Indonesian National Health Survey, 2007
N = 24.400
> 15 years
Provinces Prevalence of DM and TGT With Higher
Than The Average of National Figure
Indonesian National Health Survey, 2007
Konsensus
Pengelolaan Dan Pencegahan
Diabetes Melitus Tipe 2
Di Indonesia
2010
Perkumpulan Endokrinologi Indonesia
What should be a guidelines
! Consensus
! Evidence based
! Reasonable
! Feasible
! Attainable
! and achievable by the patients.
Who is the target of the national guidelines
! Primary care doctors
! Others health personnel
History
! The Indonesian Endocrine Society (PERKENI)
Guideline for Prevention and Management of Type
2 Diabetes had been written since 1993.
! Revised 4

times
! The latest update will be published at the end of
2010.
Variable Data
Age (Years)* (n=1719) 58.939.57
Gender** (n=1803) Male/ Female 793 (43.3) / 1010 (55.16)
Age at Onset (Years)* (n=1686) 49.686.8
Duration of Diabetes (Years)* (n=1704) 8.615.97
Type of Diabetes**
Type 1
Type 2
Others
17 (0.9)
1785 (97.5)
2 (0.1)
BMI (Kg/m
2
)
14 *
(n=1646)
<23 / !23 (%)
25.23.6
28.7 / 71.3
Duration of Treatment (Years)* (n=1817) 8.57.0
Duration of OADs (Years)* (n=1727) 8.46.8
Duration of Insulin (Years)** (n=1176) 2.83.0
Smoking (Yes)** (n=1831) 178 (9.7)
Patient Demographic and Characteristics DiabCare Indonesia 2008
* Data expressed as Mean SD; ** Data expressed as n (%); Percentage are calculated out of total cohort (n=1832) except for BMI.
Diabetes management variable Data, n (%)
Type of Management
Diet
Insulin monotherapy
Insulin and OAD combination
OAD monotherapy
Herbal
None
-
317 (17.3)
356 (19.4)
1133 (61.9)
5 (0.3)
20 (1.1)
Type of OAD Therapy
Biguanides
Sulphonylureas
Meglitinides
Alpha Glucosidase inhibitors
Thiazolidinediones
Other OADs
Traditional Herbal medicines
Double drug fixed dose combination
Triple drug fixed dose combination
1085(59.3)
1036(56.6)
8(0.4)
461(25.2)
51(2.8)
48 (2.6)
5(0.3)
88 (4.8)
5 (0.3)
Diabetes Management - The DiabCare Indonesia 2008
Diabetes management variable Data, n (%)
Insulin therapy (N=666)
Insulin analogues
Human Insulin
164 (25)
497 (74.7)
Units/day, (meanSD)
Once daily
Twice daily
More than twice daily
37.818.2
126 (18.9)
371 (55.7)
167 (25.1)
Mode of insulin administration
Pen
Syringe
Pump
631(94.7)
18(2.7)
19 (2.9)
Insulin Treatment - The DiabCare Indonesia 2008
Glycemic Control In The Study Population
Fasting Postprandial A1c
143.6 mg% 207.7 mg% 8.1 %
DiabCare Indonesia 2008
A1c and FPG stratified according to different
guidelines
DiabCare Indonesia 2008
Parameter 2003 2008
Age (Yrs) 58.79.3 58.99.5
Duration of diabetes (Yrs) 9.26.6 9.27.2
Sex (M/F) % 42.9/57.1 44/56
Type 2 DM (%) 98.2 97.4
Mean BMI (kg/m2) 24.13.5 25.13.6
Mean A1c (%) 7.92.0 8.11.6
Mean FPG (mmol/l) 8.43.4 7.92.4
Mean PPG (mmol/l) 11.63.9 11.53.6
HDL-cholesterol (mmol/l) 1.30.4 1.30.8
Triglycerides (mmol/l) 2.01.1 1.70.6
Comparison of 2003 and 2008 DiabCare study
List of Centre DiabCare Indonesia 2008
! Cipto Mangunkusumo Central Hospital,
Jakarta
! Fatmawati Hospital, Jakarta
! Husada Hospital, Jakarta
! Hasan Sadikin Hospital, Bandung
! Kariadi Hospital, Semarang
! Sardjito Hospital, Yogyakarta
! Moewardi Hospital, Solo
! Diabetes Clinic, Darmo Hospital,
Surabaya
! Private Clinic, Surabaya
Sanglah Hospital, Bali
Wahidin Sudirohusodo Hospital,
Makassar
Kandou Hospital, Manado
Moh. Husein Hospital, Palembang
Adam Malik Hospital, Medan
M Jamil Hospital, Padang
Abdul Wahab Syahranie Hospital,
Samarinda
Ulin Hospital, Banjarmasin
Saiful Anwar Hospital, Malang
Conclusions
! Poor glycaemic control in majority of patients is a
concern.
! There is a need for a large proportion of patients to be
adjusted to more intensive pharmacotherapy
! and a multi-disciplinary approach for management
should be adopted
! The study findings should be communicated to
policymakers and physicians to help them provide proper
healthcare and its facilities in Indonesia.
Konsensus
Pengelolaan Dan Pencegahan
Diabetes Melitus Tipe 2
Di Indonesia
2010
Perkumpulan Endokrinologi Indonesia
Overview
! Epidemiology diabetes in Indonesia
! History of PERKENI Guidelines
! Results of DiabCare study
! Screening and diagnosis criteria
! Diabetes management and new drugs
! Algorithm of treatment
! Blood glucose monitoring
! Conclusion
Criteria for testing for diabetes in asymptomatic adult individuals
1. Testing should be considered in all adults who are overweight (BMI > 25 kg/m2*)
and have additional risk factors:
! physical inactivity
! first-degree relative with diabetes
! members of a high-risk ethnic population (e.g., African American, Latino, Native
! American, Asian American, Pacific Islander)
! women who delivered a baby weighing > 9 lb or were diagnosed with GDM
! hypertension (> 140/90 mmHg or on therapy for hypertension)
! HDL cholesterol level < 35 mg/dl and/or a triglyceride level > 250 mg/dl
! women with polycystic ovary syndrome
! A1C > 5.7%, IGT, or IFG on previous testing
! other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis
nigricans)
! history of CVD
2. In the absence of the above criteria, testing diabetes should begin at age 45 years
3. If results are normal, testing should be repeated at least at 3-year intervals, with
consideration of more frequent testing depending on initial results and risk status.
*At-risk BMI may be lower in some ethnic groups.
Standards of Medical Care in Diabetes2010 ADA
Categories of Increased Risk for Diabetes
Testing Value
Fasting Plasma Glucose (FPG) 100 125 mg/dl : IFG
2-h PG in the 75-g OGTT 140-199 mg/dl : IGT
A1C 5.76.4%
Standards of Medical Care in Diabetes2010 ADA
Criteria for the diagnosis of diabetes (ADA)
1) A1C >6.5%. The test should be performed in a laboratory using a
method that is NGSP certified and standardized to the DCCT assay.*
OR
2) FPG >126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least
8 h.*
OR
3) Two-hour plasma glucose > 200 mg/dl (11.1 mmol/l) during an OGTT. The test
should be performed as described by the World Health Organization, using a
glucose load containing the equivalent of 75 g anhydrous glucose dissolved in
water.*
OR
4) In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a
random plasma glucose > 200 mg/dl (11.1 mmol/l).
*In the absence of unequivocal hyperglycemia, criteria 13 should be confirmed by
repeat testing.
Standards of Medical Care in Diabetes2010 ADA
Recommendation of the International Expert
Committee For Diagnosis Diabetes
! A1C assay is an accurate, precise measure of chronic glycemic levels
and correlates well with the risk of diabetes complications.
! A1C assay has several advantages over laboratory measures of glucose.
! Diabetes should be diagnosed when A1C is 6.5%. Diagnosis
should be confirmed with a repeat A1C test. Confirmation is not
required in symptomatic subjects with plasma glucose levels 200
mg/dl.
! If A1C testing is not possible, previously recommended diagnostic
methods (e.g., FPG or 2HPG, with confirmation) are acceptable.
! A1C testing is indicated in children in whom diabetes is suspected
but the classic symptoms and a casual plasma glucose 200 mg/dl
are not found.
Diabetes Care 2009 ; 32 : 1327-1334
Advantages of Proposal to Use HbA1c for Diabetes Diagnosis
Standardized and aligned to the DCCT/ UKPDS; measurement of
glucose is less well standardized
Better index of overall glycemic exposure and risk for long-term
complications
HbA1c level is not affected by short-term lifestyle changes
Substantially less biologic variability
Substantially less preanalytic instability
No need for fasting or timed samples
Relatively unaffected by acute (e.g., stress or illness related)
perturbations in glucose levels
Currently used to guide management and adjust therapy
Convenient for patients i.e. no fasting or other test preparation
required
Accurate, precise measure of chronic glycaemic levels
Lower between- and within-subject coefficients of variation and
reduced possibility of pre-analytic errors compared with glucose
Correlates with risk of diabetes defining complications (retinopathy)
Familiar test parameter i.e. already used to guide therapeutic decisions
Diabetes Care 2009; 32(7): 1327-1334
Disadvantages of Proposal to Use HbA1c for Diabetes Diagnosis
Relationship between HbA1c and glucose, whilst good, is not
perfect
Whilst existing glucose based diagnostic criteria remain
valid, the current proposal does not advocate a confirmatory
check of glucose at any stage
Point of care instruments currently considered inadequate for
diagnostic purposes
Methods suffer from multiple interferences that clinicians
may not be aware of
The proposed cut-off of 6.5% is predictive of retinopathy
but is it the most appropriate outcome on which to choose a
diagnostic target?
Not appropriate for diagnosis of gestational diabetes
Upper limit of normal HbA1c (6.0%) leaves a diagnostic
hiatus between 6.1 and 6.5%, in addition to a discrepancy
between the typical treatment target of <7% and the
diagnostic level
Racial disparities in HbA1c may exist that are independent of
blood glucose
Diabetes Care 2009; 32(7): 1327-1334
Proposed Criteria for Screening and
Diagnosis of Diabetes
J Clin Endocrinol Metab 2008 ; 93: 24472453
Diagnostic criteria for diabetes mellitus
1. Classic symptoms of diabetes + random glucose plasma
level ! 200 mg/dL . Random glucose plasma level is a
test which access glucose plasma level at a single time
without concerning about last meal schedule.
or
2. Classic symptoms of diabetes + Fasting plasma glucose !
126 mg/dL. Fasting means patients not getting intake
calories for minimum 8 hours.
or
3. 2-h plasma glucose at glucose tolerance test ! 200 mg/
dL. Glucose tolerance test done by the WHO standard
using 75 g anhydrous glucose which solvent in the 100 cc
water.
PERKENI Guideline 2010
Kadar glukosa darah sewaktu dan puasa sebagai
patokan penyaring dan diagnosis DM (mg/dL)
Bukan DM Belum pasti
DM
DM
Kadar glukosa
darah
sewaktu
Plasma
vena
<100 100 -199 >200
Darah
kapiler
< 90 90-199 >200
Kadar glukosa
darah puasa
Plasma
vena
<100 100-125 >126
Darah
kapiler
< 90 90-99 >100
Catatan :
Untuk kelompok risiko tinggi yang tidak menujukkan kelainan hasil dilakukan ulangan
tiap tahun. Bagi mereka yang berusia >45 tahun tanpa faktor risiko lain, pemeriksaan
penyaring dapat dilakukan setiap 3 tahun.
PERKENI GUIDELINES 2010
PERKENI GUIDELINES 2010
Overview
! Epidemiology diabetes in Indonesia
! History of PERKENI Guidelines
! Results of DiabCare study
! Screening and diagnosis criteria
! Diabetes management and new drugs
! Algorithm of treatment
! Blood glucose monitoring
! Conclusion
Treatment Algorithm for Type 2 Diabetes in Indonesia
The Indonesian Society of Endocrinology, 2006
! Principles in selecting antihyperglycemic
interventions:
! Effectiveness in lowering glucose
! Extraglycemic effects that may reduce long-
term complications
! Safety profiles
! Tolerability
! Ease of use
! Expense
Nathan DM, et al. Diabetes Care 2009;32 193-203.
L
I
S
T
O
F
O
A
D
2006
33
Expected HbA
1c
reduction according
to intervention
Intervention Expected ! in HbA
1c
(%)
Lifestyle interventions 1
to
2%
Metformin 1 to 2%
Sulfonylureas 1 to 2%
Insulin 1.5 to 3.5%
Glinides 1

to 1.5%
1
Thiazolidinediones 0.5 to 1.4%
"-Glucosidase inhibitors 0.5 to 0.8%
GLP-1 agonist 0.5 to 1.0%
Pramlintide 0.5 to 1.0%
DPP-IV inhibitors 0.5 to 0.8%
1. Repaglinide is more effective than nateglinide
Adapted from Nathan DM, et al. Diabetes Care 2009;32:193-203.
Comparative Effectiveness and Safety of Oral
Medications for Type 2 Diabetes Mellitus
Compared with newer agents, metformin and
second-generation sulfonylureas share 3
additional advantages:
! lower cost,
! longer use in practice,
! more intensive in long-term trials with
clinically relevant end points.
Ann Intern Med. 2007;147:386-399.
35
Inhibition of DPP-4 Increases Active GLP-1
GLP-1
inactive
(>80% of pool)
Active
GLP-1
Meal
DPP-4
Intestinal
GLP-1
release
GLP-1 t
!
=12 min
DPP-4=dipeptidyl peptidase-4; GLP-1=glucagon-like peptide-1
Adapted from Rothenberg P, et al. Diabetes. 2000; 49(suppl 1): A39. Abstract 160-OR.
Adapted from Deacon CF, et al. Diabetes. 1995; 44: 1126-1131.
Vildagliptin Effective across Hyperglycemia Spectrum
BL HbA1c
"8%
n= 1569 543 490 362 174
BL=baseline; HbA1c-hemoglobin A1c; vilda=vildagliptin
*P <0.001 from BL. HbA1c change from baseline to Week 24 (end point)
pooled monotherapy intention-to-treat / primary intention-to-treat population.
Data on file, Novartis Pharmaceuticals.
Vilda 50 mg twice daily
BL= 8.7 7.6 8.5 9.5 10.6
C
h
a
n
g
e

f
r
o
m

B
L

i
n

H
b
A
1
c

(
%
)

8< HbA1c
"9%
9< HbA1c
"10%
HbA1c
>10%
*
*
*
*
Overall
*
! Evidence generated from a comprehensive clinical program of
>20,200 patients
a

! A potent, highly selective, and reversible DPP-4 inhibitor
! Robust efficacy
! sustained efficacy over 2 years
! efficacy comparable with TZD and acarbose in monotherapy (at 24 weeks)
! efficacy demonstrated in IGT population
! Excellent tolerability
! low risk for hypoglycemia
! superior GI tolerability versus metformin
! no weight gain overall
! weight loss relative to TZD
! incidence of edema similar to placebo
! overall incidence of AEs comparable with placebo
! No drug-drug interaction with commonly prescribed agents
Vildagliptin: Summary for Monotherapy
AE=adverse event; DPP-4=dipeptidyl peptidase-4; GI=gastrointestinal; TZD=thiazolidinedione
a
20,200 represents the overall patient numbers included in studies for monotherapy and combination therapy.
DPP-IV Inhibitor for Glycemic Control
AACE/ACE algorithm
DPP-IV inhibitors can be given at any level of A1C, as a
monotherapy, dual therapy, or triple therapy.
Endocr Pract. 2009;15(6):540-59
PERKENI guideline 2010
DPP-IV inhibitor was included in one of the oral medications for
diabetes. These drugs consumed together with or before meals
and can be given as monotherapy or dual therapy combined
with modification lifestyle.
Exenatide (Exendin-4)
39amino acid peptide
incretin mimetic that
exhibits glucoregulatory
activities similar to the
mammalian incretin
hormone GLP-1
- Well tolerated
- Reduce A1C with no weight
gain
- No increased incidence of
hypoglycemia in T2DM
- Causes a relatively high
frequency of gastrointestinal
disturbances (transitory)
Diabetes Care 28:1092-100, 2005
DIAGNOSIS TAHAP-1
(Mono-Terapi)
TAHAP-2
(Kombinasi 2 obat)
TAHAP-3
(Insulin intensif)
DIABETES GSH +
Metformin
Atau salah satu
dari:
SU, AGI, Glinid,
TZD, DPP-IV inh
GSH +
Metformin
Ditambah salah
satu dari:
SU, AGI, Glinid,
TZD, DPP-IV inh
Kombinasi 3 obat
GSH +
Metformin
Ditambah dua
diantara:
SU, AGI, Glinid,
TZD, DPP-IV inh
Insulin intensif
Basal plus atau
Basal bolus
Mencapai target HbA1C <7%
TERUSKAN
Catatan:
- GSH: gaya hidup sehat, SU: sulfonilurea, AGI: alfa glukosidase inhibitor, TZD: tiazolidindion, DPP-IV inh: dipeptidil peptidase inhibitor
- Kombinasi 3 obat hanya diberikan bila penyandang DM (diabetisi) menolak insulin
- Untuk terapi insulin " lihat konsensus insulin PB PERKENI
2-3 bulan gagal
2-3 bulan
gagal
2-3 bulan
gagal
HbA1C 8-9% >9% 9-10% >10% <7% Catatan: 7-8%
GHS
GHS (Gaya
Hidup Sehat):
Penurunan
berat badan
Mengatur diit
Latihan
jasmani teratur
GHS
+
Monoterapi
Met, SU,
AGI, Glinid,
TZD, DPP-
IV
GHS
+
Kombinasi
2 obat
Met + SU,
AGI, Glinid,
TZD, DPP-
IV
GHS
GHS
+
+
Kombinasi
3 macam
obat
Kombinasi
2 macam
obat
Met + SU,
AGI, Glinid,
TZD, DPP-
IV
Met + SU,
AGI, Glinid,
TZD, DPP-
IV
+
Basal
Insulin
GHS
+
Insulin
Intensif
1. Dinyatakan
gagal apabila
dengan terapi
2-3 bulan tidak
mencapai
target HbA1C
<8%
2. Bila tidak ada
pemeriksaan
HbA1C dapat
dilakukan
pemeriksaan
rata-rata
glukosa darah
sehari dan
dikonversikan
ke HbA1C
menurut
kriteria ADA
2010
Algoritma pengelolaan DM tipe 2 tanpa disertai dekompensasi alternatif terutama untuk internist
Belum
dianjurkan
Diabetes Prevention
Overview
! Epidemiology diabetes in Indonesia
! History of PERKENI Guidelines
! Results of DiabCare study
! Screening and diagnosis criteria
! Diabetes management and new drugs
! Algorithm of treatment
! Blood glucose monitoring
! Conclusion
Self Monitoring of Blood Glucose
! To evaluate individual response to therapy
and assess whether glyceamic targets are
being achieved.
! Useful in preventing hypoglycemia and
adjusting medications (particularly prandial
insulin doses), medical nutrition therapy,
and physical activity.
Standards of Medical Care in Diabetes-2010.
Self Monitoring of Blood Glucose
! Patients starting basal insulin therapy at bedtime or initiating
premixed insulin therapy before dinner should monitor the
morning fasting blood glucose levels daily.
! Patients with T1DM and pregnant women taking insulin "
SMBG is recommended three or more times daily
! The optimal frequency and timing of SMBG for patients
with type 2 diabetes on noninsulin therapy is unclear
Standards of Medical Care in Diabetes-2010.
Self Monitoring of Blood Glucose (SMBG)
Tools to assess treatment in diabetic patients that is
recommended especially in:
1. Patients that will undergo insulin therapy
2. Patients receiving insulin therapy
3. Patients with A1C level did not reach the target
4. Women planned for pregnancy / pregnant women
with hyperglycemia,
5. Patients with recurrent hypoglycemia.
PERKENI Guidelines 2010
Target of Treatment
Risk CVD (-) Risk CVD (+)
IMT (kg/m
2
) 18,5 - < 23
Glukosa darah
- Puasa (mg/dL) < 100
- 2 jam PP (mg/dL) < 140
A1C (%) < 7,0 < 7,0
Tekanan Darah < 130/80 < 130/80
Profil Lipid
Total kolesterol (mg/dL)
Trigliserid (mg/dL)
HDL kolesterol (mg/dL)
LDL kolesterol (mg/dL) < 100 < 70
PERKENI Guidelines 2010
In conclusion
! In the forthcoming national guideline on the
Prevention and Management of Type 2 DM,
PERKENI already update several critical issues
such as the screening and diagnostic criteria,
target of treatment, algorithm of management,
and blood glucose monitoring.
! We also aware that to improve quality of diabetes
care in Indonesia, the written guidelines should
be followed by the activities of capacity building
for all health personnel and the facilities
improvement of health care for diabetes mellitus
! A multi-disciplinary approach for management
should be adopted