Curriculum Vitae

Nama : ROCHSISMANDOKO
Tempat / Tgl lahir : Lahat,27 September 1957
Alamat Rumah : De Park,Cluster Cajuputi
Blok AC 2/3, BSD City
Riwayat pendidikan :
1. Dokter Umum,FK UNSRI, 1984
2. Spesialis Penyakit Dalam, FK UNSRI 1994
3. Konsultan Endokrin Metabolik dan Diabetes,FKUI,2009

Riwayat pekerjaan :
1. Puskesmas Ds Toari,Kab.Kolaka,Prov.SulawesiTenggara,19851988
2. RSUP Palembang, 1988 1994
3. RSUD Dr.M.Azhari,Kab.Pemalang,Prov.Jawa Tengah,1994 - 1999
4. RSUP Persahabatan,1999-sekarang
5. Dosen Pendidik Klinis FKUI
6. Garuda Indonesia
7. Bethsaida Hospital, Paramount Serpong,Tangerang
Organisasi : Ketua Perkumpulan Edukator doabetes Indonesia
Ketua Persatuan Diabetes Indonesia wilayah banten
Strike The Spike!
Strategies for Combatting
After-Meal Highs
Rochsismandoko
RSUP Persahabatan, Jakarta
The question is not whether to
target postprandial,
preprandial or fasting
glycemia, but when, how, and
to what goals.
 After-Meal Peaks Defined

The net rise that occurs

300 from before eating to the
+ 140
250 highest point after eating.

200 ADA Goal::<180 mg/dl 1-2 hrs after

start of meal
150 DCCT Goals: <180 mg/dl 2 hrs
after meal
100
European Diabetes Policy Grp:
<165 (to prevent complications)
What are appropriate goals?

HbA1c
FPG
2 hr PPG
Normalization of Glycemia
To achieve a normal or near normal
HbA1c, both FPG and PPG levels
must be normal or near normal.

Thus both FPG and PPG must be

targets for therapy

Nevertheless, might there be

situations in which it is preferable to
treat one or the other first ???
 Patients With Type 2 Diabetes May Spend More Than
12 Hours per Day in the Postprandial State

Postprandial Postabsorptive Fasting

Duration of postprandial state

Breakfast Lunch Dinner Midnight 4 AM Breakfast

8 AM 11 AM 2 PM 5 PM

Adapted from Monnier L. Eur J Clin Invest. 2000;30(suppl 2):3-11.

 As Patients Get Closer to A1C Goal,
the Need to Successfully
Manage PPG Significantly Increases
Increasing Contribution of PPG as A1C Improves
100%
30%
80%
50%
Contribution

60% 55%
70%
60%
FPG
%

40% PPG
70%
45% 50%
20% 40%
30%

0%
< 10.2 10.2 to 9.3 9.2 to 8.5 8.4 to 7.3 < 7.3
A1C Range (%)

Adapted from Monnier L, Lapinski H, Collette C. Contributions of fasting and

postprandial plasnma glucose increments to the overall diurnal hyper glycemia
of Type 2 diabetic patients: variations with increasing levels of HBA(1c).
Diabetes Care. 2003;26:881-885.
Contribution of Postprandial BG to HbA1C
100

*=p<0.05vs HbA1c <6.2 %

*
80
*
Contribution (%)

60 *
*
*
40

20

0
4.7-6.2 6.2-6.8 6.8-7.3 7.3-7.8 7.8-8.9 8.9-15.0
HbA1c sixtiles(%)

Woerle HJ et al Diabetes Res Clin Pract. 2007 Jan 19

 Relative risk for death increases with
2-hour blood glucose irrespective of
the FPG level

2.5

2.0
Hazard ratio

1.5

1.0
11.1
0.5 7.811.0

0.0 <7.8
<6.1 6.16.9 7.0
Fasting plasma glucose (mmol/l)
Adjusted for age, center, sex
DECODE Study Group. Lancet 1999;354:617621
Hoorn Study 2-h glucose better predictor of mortality
than HbA1c
Honolulu Heart 1-h glucose predicts coronary heart disease
Program
Chicago Heart Study 2-h postchallenge glucose predicts all-
cause mortality
DECODE High 2-h postload BG is associated with
increased risk of death, independent of
fasting glucose
Coutinho et al. 2-h glucose associated with CHD
Whitehall Study, Paris 2-h postchallenge glucose predicts all-
Prospective Study, cause and CHD mortality
Helsinki Policemen
Study
Diabetes Intervention Postmeal but not fasting glucose is
Study associated with CHD
 Long-Term Problems
52 Type 1s, similar BP between groups

Post-prandial Time to onset of

Range
glucose proteinuria
Persistent <200 110-198 23 yrs
Intermittent >200 118-228 19 yrs
Persistent > 200 201 + 14 yrs
Source: Kidney Intl. 1987; 32 (supp 22): S53-
 Long-Term Problems
% Progression of Diabetic Retinopathy in Type-2 Diabetes
(independent of HbA1c)

70%
60%
50%
40% ppg >275
30% ppg 210-275
20%
10% ppg <210
0%
ppi < 108 ppi 108-210 ppi > 210

Source: Osaka Univ. School of Medicine. Diabetes Care (28): 11, 2806.
 So How Can We Assess Post-Prandial
Glucose Control Clinically ??
Frequent fingersticks
HbA1C
Fructosamine
Continuous Glucose
Monitoring Systems
Historical
Real-time
1,5 Anhydroglucitol
 Approaches/Agents That Address
Postprandial Hyperglycemia
Meglitinides
Alpha-Glucosidase Inhibitors
Prandial Insulin
GLP-1 analogues
DPP-IV inhibitors
Pramlintide
Glycemic Index/Load
Acute hyperglycemia potentially contributing
to the development of diabetic complications.

Increased GFR and renal plasma flow;

Increased retinal blood flow;
Reduction of motor and sensory nerve
conduction velocity;
Impairment of endothelial NO-mediated
function; procoagulative state;
Increase in adhesion proteins;
Oxidative stress;
Protein labile glycation

G. Paolisso et al.

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EVIDENCE STATEMENTS
Postmeal hyperglycaemia are independently
associated with the following in people with DM
macrovascular disease
retinopathy
cancer
impaired cognitive function in elderly people
with type 2 diabetes
increased carotid intima-media thickness
decreased myocardial blood volume and
myocardial blood flow
oxidative stress, inflammation and endothelial
dysfunction
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1. Does tighter glycemic control
matter?
2. How does postprandial glucose
relate to overall glycemic levels?
3. Is postprandial glucose control an
independent contributor to diabetes
outcomes?
4. Is postprandial glucose control safe
for most patients?
5. Is postprandial glucose control
practical in primary care settings?
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Does tighter glycemic control matter?

26
How does postprandial glucose
relate to overall glycemic levels?
Bonora et al showed that A1C levels are more closely related to
preprandial than to postprandial glucose levels, even though
the majority of patients studied had extremely elevated glucose
excursions with meals and extended periods of postprandial
hyperglycemia

In contrast, Avignon et al found that post-lunch plasma

glucose and extended post-lunch plasma glucose was more
reliable in predicting poor glycemic control than pre-
breakfast or pre-lunch plasma glucose.

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The first step in the deterioration of glucose
homeostasis is the loss of postprandial glycemic
control, which is followed by a progression to
morning hyperglycemia and eventually to sustained
nocturnal hyperglycemia

Impaired glucose tolerance is considered a

prediabetic stage, and it may occur years before
elevated fasting plasma glucose (FPG) levels are
observed, defined as 2-hour pp between 140 and
199 mg/dL

Postprandial hyperglycemia can be the rate-limiting

factor for achieving optimal glycemic control. 28
In a study of patients with type 2 diabetes with secondary
failure of sulfonylurea therapy, Feinglos et al.18 showed that
improvement of postprandial hyperglycemia, using insulin
lispro (Humalog) at mealtime in combination with a
sulfonylurea, not only reduced 2-h postprandial glucose
excursions, but also reduced both fasting glucose and A1C
levels from 9.0% to 7.1% (P < 0.0001). s.

Regardless of whether postprandial glucose is a better

predictor of A1C than fasting/preprandial glucose, most
researchers agree that the best predictor of A1C is mean
blood glucose, which is a composite of both
fasting/preprandial and postprandial glucose. Therefore, it
is reasonable to conclude that achieving near-normal
postprandial glucose levels is essential to achieving overall
glycemic control
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Is postprandial glucose control an independent
contributor to diabetes outcomes?
The Honolulu Heart Study : strong correlation between
postchallenge glucose levels and cardiovascular mortality.
The Diabetes Intervention Study :moderate pp hyperglycemia to
be more indicative of artherosclerosis than was fasting glucose,
and found postprandial but not fasting glucose to be an
independent risk factor for cardiovascular mortality.
The DECODE Study :
increased mortality risk associated with 2-h postglucose load
plasma levels than with fasting plasma glucose.
De Vegt et al :
The degree of risk conferred by the 2-h postprandial glucose
concentration was nearly twice that conferred by A1C level
Recent studies :even moderate pp hyperglycemia (148199
mg/dl) more indicative of artherosclerosis also may have direct
30
adverse effects on the endothelium
Is postprandial glucose control safe for
most patients?
The safety of postprandial glucose control is both dependent
upon the therapy used and specific to each patients ability to
recognize and treat hypoglycemia when it does occur.
The VA Cooperative Study : severe hypoglycemic extremely
rare among intensively treated,not significantly different from
those among conventionally treated
The Kumamoto study : no severe hypoglycemia over 8 years
in either the intensively or the conventionally treated group.
The UKPDS : severe hypo in intensively treated from 0.1 to
2.3% per year, depending on the therapy, severe hypo
(0.03% per year) was also reported by patients treated with
diet therapy alone
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Is postprandial glucose control safe for
most patients?
The risk of severe hypo in type 2 DM is significantly
less than in type 1 DM because deficits in secretion of
counter-reg. hormones(glucagon,epinephrine) are
less prominent in type 2

Glucose thresholds for counter-reg.hormone

secretion are altered both in well-controlled and
poorly controlled type 2 Counter-reg.hormone release
occur at normal glucose values
Spyer et al.concluded that this effect may protect
patients with type 2 diabetes against severe
32
hypoglycemia
Is postprandial glucose control practical in
primary care settings?
strategies useful in initiating more aggressive
postprandial glucose management :
.1.Make appropriate use of qualified DM education program
2. Establish aggressive, but realistic glycemic goals for
each patient
3. Match and continuously adjust th/ to the each patient.
4. Utilize laboratory and SMBG data to determine
appropriate therapy, then make th/ adjustments on a t
timely basis
5. Monitor and treat all diabetes risk factors.

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Tool Postprandial
DescriptionHyperglycemia
Drawbacks Assessment
Tools
HbA1C Mean of last Can mask extremes; cannot change quickly
60-90 days Interferences (hemoglobinopathies)
Individual variability in glycosylation rates
Fructosamine Mean of last Can mask extremes
3-4 weeks Individual variability in glycosylation rates
Oral Glucose Tolerance Multiple data points Good measure of postprandial glucose but time-
Test (75 gr load) on one day consuming for patients and providers
Only measures one day in time so could be skewed
by illness or stress
Continuous Glucose 24/7 continuous Excellent tool but cost and reimbursement is issue
Monitors blood glucose for T2D and some T1D
measurements Time-consuming training and report review
Some patients will not wear sensor 24/7
Frequent Fingerstick Single data points Can miss peaks due to timing
Blood Glucoses Patient adherence to frequent PPG testing
Cost and insurance limits on BG strip quantity
Unreadable/inaccurate glucose logbooks
1,5-Anhydroglucitol 1-2 week measure Not accurate in advanced kidney or liver disease
(1,5-AG; GLYCOMARK) of average peak Individual variability in renal thresholds especially
blood glucose during pregnancy
 After-Meal Spike Reduction
Meal choices
Lifestyle Approaches
Medicinal Approaches
 Glycemic Index
All carbs (except fiber) convert to blood glucose
eventually
G.I. Reflects the magnitude of blood glucose
rise for the first 2 hours following ingestion
G.I. Number is % or rise relative to pure
glucose (100% of glucose is in bloodstream
within 2 hours)
 Glycemic Index
Use of Glycemic Index Fastest Glucose
Lower GI foods digest & Dextrose

convert to glucose more slowly Starch (branched-chain)

Sucrose/Corn Syrup
High-fiber slower than low Fructose
Hi-fat slower than low Starch (straight-chain)
Lactose
Solids slower than liquids
Galactose
Cold foods slower than hot Slowest Sugar Alcohols

Type of sugar/starch affects GI

 Glycemic Index

Slow Stuff Average Stuff Fast Stuff

Pasta Fruit Breads/Crackers
Legumes Juice Salty Snacks
Salad Veggies Pizza Potatoes
Dairy Soup Rice
Chocolate Cake Cereals
Sugary Candies
Physical Activity Intervention
Muscle Use Soon After Eating

Accelerated Delayed Glucose Uptake/

Insulin Absorption Digestion Utilization

Improved After-Meal Control

 OLAH RAGA
FITT : Frekwensi, Intensitas, Takaran
waktu, Tipe olah raga(aerobik terbaik)

Frekwensi : 3-5 kali(total 150 mt) / minggu

Jangan lebih dari 2 hari tanpa olah raga

Intensitas : ringan sedang (Target 60-

70% DJM ); DJM = 220 usia

Takaran waktu : 30 60 menit

Tipe: aerobik (jalan,sepeda, renang, senam )
Multiple, Complex Pathophysiological
Abnormalities in T2DM
GLP-1R
agonists Insulin
pancreatic
Glinides S U s insulin
incretin
effect secretion
DPP-4 Amylin pancreatic
inhibitors mimetics glucagon
_ secretion DA
agonists
AGIs
?
Gut CH delivery
& absorption HYPERGLYCEMIA
Metformin TZDs
_
Bile acid
sequestrants

+ peripheral
hepatic renal glucose
glucose glucose uptake
production excretion
SGLT2 Inhibitors Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011
Summary of Glucose Lowering Intervention
Intervention DM type 2 Hyperglycemia Expected decrease
Pathogenesis target in A1C (%)
Lifestyle Insulin resistance Basal Prandial 12
Modification
Insulin Insulin resistance Basal Prandial 1,5 3,5
B cell dysfunction
Metformin Insulin resistance Basal Prandial? 12

Sulfonilurea B cell dysfunction Basal Prandial 12

Acarbose Delay glucose absorption Prandial 0,5 0,5

Glinide B cell dysfunction Prandial 0,5 1,5

Pioglitazone Insulin resistance Basal Prandial 0,5 1,4

DPP-4 inhibitors cell dysfunction Basal Prandial 0,5 0,8

Insulin secretion
GLP-1 agonist cell dysfunction Basal Prandial 0,5 1
Insulin secretion
Slide 42
Nathan et al. ASA and EASD A Consensus Algorithm. Diab care 2009; 32:193 EASD and ESC 2007