Postprandial

1. Postprandial Hyperglycemia
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2. Outline
Diabetic Explosion in India
Indian Lifestyle – Changing Scenario
Post-Prandial Hyperglycemia – The dark face!
Management of Post-Prandial Hyperglycemia
Summary
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3. 3
“DIABETIC
EXPLOSION”
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4. “70 million diabetics in India by ’15: A Study”
‘Diabetic Explosion ‘ Due to Changing Lifestyle
Aren't we aware of it ???
Then ???
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5. Diabetes – An Epidemic…
According to Diabetes Atlas published in 2007, there are 246 million diabetics
across the world, with 80% of them in developing and underdeveloped
countries.
India has 40.9 million diabetics with a prediction of 69.9 million by 2015.
An observation reveals that, there is 40% increase in prevalence in urban areas
in 6 years whereas, 49% increase in merely 3 years in rural areas.
This shift according to Endocrine Diagnostic Centre & Diabetes Care is due to
Changing Lifestyle and Genetic factors!!!
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6. Along with it…
“The global prevalence of diabetes is set to double over the next 25 years.
 Developing countries like India, already top of the diabetes league, are expected to
shoulder much of this burden.
Epidemiological studies show that the prevalence of diabetes is particularly high in urban
areas in India.
Cities are also home to a large pool of people with a great risk of developing diabetes in
the future.”
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7. What is driving Diabetes Epidemic in
INDIA???
OR
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8. What are appropriate goals?
HbA1c
FPG
2 hr PPG
Normalization of Glycemia
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9. Glycemic Targets in Clinical Practice:
Postprandial vs Preprandial
and Fasting?
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10. 10
POST PRANDIAL
HYPERGLYCEMIA –
THE DARK FACE
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11. Have a look at this…
Mr. Sunil Agarwal, software engineer of age 32 years is a resident of
Delhi
Family Details –
Married, a son of 3 years
Father – Diabetic Patient
Mother – Died due to Heart Attack
Personal Details –
Weight – 82 kgs
Smoker (5-7 cigarettes/day)
Drinks occasionally
Diet pattern – Nonvegetarian, but irregular meal pattern
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12. Case Contd…
On the World Heart Day, his software firm was having free
BP and Blood Glucose check up camp.
His report revealed –
BP – 124/82 mmHg
FPG – 117 mg/dl
PPBG – 276 mg/dl
He was shocked with the reports and he decided to visit his
family physician.
His family physician confirmed him as patient of IGT with
Postprandial Hyperglycemia
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13. Post Prandial Hyperglycemia
Independent risk factor for cardiovascular disease
Increases earlier and faster than plasma glucose levels
Contributes more to HbA1c than to fasting glucose at A1c levels below 8.5%
Rate limiting factor for achieving adequate glycemic control
Harmful acute effects
Endothelial dysfunction
Increase in oxidative stress
Increases the inflammatory milieu
Increase in protein glycosylation
Coagulation affected
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14. Post Prandial Glucose Disposal in Type 2
Diabetes
Lack of appropriate suppression of endogenous glucose
release
Both gluconeogenesis & glycogenolysis
Normal total tissue glucose uptake
Decreased tissue glucose clearance
Decreased glucose oxidation
Increased nonoxidative glycolysis
Increased glycogen cycling
Increased glucose uptake by alternative tissues
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15. Adapted from Monnier L. Eur J Clin Invest. 2000;30(suppl 2):3-11.
Duration of postprandial state
BreakfastLunch Dinner Midnight4 AMBreakfast
8 AM 11 AM 2 PM5 PM
Postprandial Postabsorptive Fasting
Patients With Type 2 Diabetes May Spend More
Than 12 Hours per Day in the Postprandial State
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16. 0
2
4
6
8
10
12
14
16
0 5 10 15 20 25
2 hr after OGTT plasma glucose (mmol/l)
2 hr after SMM plasma glucose (mmol/l)
0
2
4
6
8
10
12
14
16
0 5 10 15 20 25
2 hr after OGTT plasma glucose (mmol/l)
2 hr after SMM plasma glucose (mmol/l)
Correlation between plasma glucose levels after
OGTT and standard mixed meal
Wolever TMS et al. Diabetes Care 1998;21:336–40
r=0.97r=0.97
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17. Changes in Postprandial Glucose Metabolism in
Type 2 DM
Use triple isotope technique and indirect calorimetry
DM pts had:
increased overall glucose release
Increased gluconeogenesis and glycogenolysis
~90% of the increased glucose release occurred in the first 90
min post-prandial
In DM glucose clearance and oxidation were reduced
Non-oxidative glycolysis was increased
Net splanchnic glucose storage was reduced ~ 45% d.t. increased
glycogen cycling
Woerle HJ et al Am J Physiol Endocrinol Metab 200617 [email protected]

18. Relationship between HbA1C, FPG and 2 h. PPG
Van Haeften T et al Metabolism 2000Van Haeften T et al Metabolism 2000
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19. Increasing Contribution of PPG as A1C Improves
30%
40%
45%
50%
70%
60%
55%
50%
30%
70%
0%
20%
40%
60%
80%
100%
< 10.210.2 to 9.39.2 to 8.58.4 to 7.3< 7.3
A1C Range (%)
%
Contribution
FPG
PPG
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.
As Patients Get Closer to A1C Goal, the Need to
Successfully Manage PPG Significantly Increases
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20. Post-Prandial Hyperglycemia Antecedes Fasting
Hyperglycemia
Monnier L et al Diabetes Care 30:263-269, 2007
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21. PPG, but not FPG distinguishes patients with HbA1C
Between 6.0-7.0%
Characteristics
# of patients
Gender
Age
BMI
FPG
2hPPG
Mean HbA1C
6.0-6.5 6.6-7.0
37 16
14/23 8/8
54.6 49.6
27.8 27.9
111 113 (p=0.88)
198 226 (p=0.03)
6.26 6.73
HbA1C Group (%)
Woerle HJ et al Arch Intern Med. 2004;164:1627-1632.21 [email protected]

22. <6.1 6.1–6.9 ³7.0
³11.1
7.8–11.0
<7.8
Fasting plasma glucose (mmol/l) 2-hour plasma glucose
(mmol/l)
2.5
2.0
1.5
1.0
0.5
0.0
Hazard ratio
Adjusted for age, center, sex
DECODE Study Group. Lancet 1999;354:617–621
Relative risk for death increases with 2-hour blood
glucose irrespective of the FPG level
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23. Relationship Between HbA
1c
, FPG and PPG in Treated
T2DM Patients
Major
HbA
1c
(%) FPG (mM) PPG (mM) Problem
5 5.1 7.0-
6 6.3 8.4PPG
7 7.5 9.8PPG
8 8.7 11.2 FPG+PPG
9 9.9 12.6 FPG+PPG
10 11.1 14.0 FPG
Woerle et al., 2006.
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24. Long-Term Problems
Post-prandial
glucose
Range
Time to onset of
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-S56
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25. 22-yr CVD Mortality Risk by Baseline post-challenge glucose
Source: Chicago Heart Study, Lowe et al, Diabetes Care, 1997; 20: 163-170.
25
Long-Term Problems
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26. Effects of Reducing PPHG
-36
-34
-49
-60
-50
-40
-30
-20
-10
0
% Reduction
Risk of
progression to
diabetes
Risk of
cardiovascular
events
Risk of
development of
new cases of
hypertension
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27. Post Prandial Hyperglycemia
Rationale for treating PPHG :
 Postprandial blood glucose better predictor of glycaemic control than
FPG
 PPHG associated with microvascular complications e.g. Retinopathy,
Nephropathy etc.
 Recognized risk factor for CAD e.g. MI, death
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28. Postprandial Hyperglycemia (PPHG) :
Management
 The higher the plasma glucose level with which

a patient goes to bed as
a result of postprandial hyperglycemia,

the higher will be the fasting
hyperglycemia in the morning.

 Similarly, the higher the fasting hyperglycemia in the morning,

the higher
postprandial hyperglycemia will be during the day.

 Thus, maneuvers that primarily target fasting hyperglycemia

might not
be successful in normalizing fasting plasma glucose

levels and achieving
satisfactory HbA
1c
levels if postprandial

hyperglycemia persists.
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General Considerations
John E. Gerich, MD. Arch Intern Med. 2003;163:1306-1316. [email protected]

29. Non pharmacologic Interventions
In individuals with IGT and

in those with type 2 diabetes with suboptimal,
but not awful,

glycemic control (eg, HbA
1c
7.0%-8.0%), simple lifestyle
modifications

such as exercise, weight reduction, or change in diet
composition

can be particularly helpful.
For example, several studies have

demonstrated that weight-reducing diets
and exercise can normalize

glucose tolerance in individuals with IGT and
reduce the risk

of their developing type 2 diabetes.
Similarly, reducing

the consumption of meals containing high glycemic index
items

(eg, rice and potatoes vs pasta) can lower postprandial plasma

glucose increments as well as the average 24-hour plasma glucose

concentration.
John E. Gerich, MD. Arch Intern Med. 2003;163:1306-1316. 29 [email protected]

30. Approaches/Agents That Address Postprandial
Hyperglycemia
Meglitinides
Alpha-Glucosidase Inhibitors
Prandial Insulin
GLP-1 analogues
DPP-IV inhibitors
Pramlintide
Glycemic Index/Load
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31. Objective - Voglibose, an -glucosidase inhibitor, could prevent the
α
development of type 2 diabetes in high-risk Japanese individuals with
impaired glucose tolerance was assessed.
Trial Method - 1780 patients randomly assigned to oral Voglibose 0·2 mg
three times a day (n=897) or placebo (n=883) in a multicentre, double-
blind, parallel group trial.
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32. Results & Conclusion
0
100
200
300
400
500
600
700
Voglibose Placebo
Pts achieved normoglycemia
Pts achieved
normoglycemia
Voglibose, in addition to lifestyle modification, can reduce the development of
type 2 diabetes in high-risk individuals with impaired glucose tolerance.
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33. Br J Clin Pharmacol / 66:2 / 318–319
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34. Results & Conclusion
Voglibose treatment prevented the increase of body weight induced by Pioglitazone in
Type 2 diabetes patients.
Thus, Voglibose may be a potentially useful drug for increasing the benefit of
Pioglitazone treatment by controlling body weight.
Br J Clin Pharmacol / 66:2 / 318–319
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35. Conclusions
Hyperglycemia is an important risk factor for both microvascular

and
macrovascular complications of diabetes.
Considerable recent

evidence has accumulated, indicating that isolated
postprandial

hyperglycemia (ie, 2-hour postprandial levels >140 mg/dL

and
fasting levels <110 mg/dL) is common and is an independent

clinically
significant risk factor for CVD.
 The key factor responsible

for postprandial hyperglycemia is impaired
early insulin secretion.


Fortunately, treatment modalities are now available that

specifically target
postprandial hyperglycemia by improving

early postprandial plasma insulin
levels (eg, meglitinides,

rapid-acting insulin analogues) and several new ones
are in

development (eg, inhaled insulin and GLP-1 agonists).

John E. Gerich, MD. Arch Intern Med. 2003;163:1306-1316.
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36. Thank You
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