dr. yash pal munjal - welcome to apidsc · pdf filedr. yash pal munjal md, ficp, mams, frcp...
TRANSCRIPT
![Page 1: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/1.jpg)
Dr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA)
FIACM, FIAMS, FIMSA
• Served API as Past President, Past Dean
• Editor in Chief – API Textbook of Medicine – 9th & 10th Editions
• Around 50 publications to his credit
• Orations, like Presidential Oration, Dean’s Oration, Rabindra Nath Tagore Oration
• Principal Investigator in many multicentric as well as multinational trials
• Advisory Committees of prestigious journals like Indian Heart Journal, JAPI, Journal of Clinical
Diabetology, Indian Journal of Clinical Medicine etc.
Medical Director, Banarsidas Chandiwala Institute of Medical Sciences
Chief Consultant, Centre for Diabetes & Lifestyle Diseases, Kalkaji, New Delhi
![Page 2: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/2.jpg)
![Page 3: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/3.jpg)
Currently Available Glucose Monitoring Tests
•Monitoring of Blood Glucose (MBG)
•Glycosylated Hemoglobin (HbA1c)
![Page 4: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/4.jpg)
Glycemic Variability
![Page 5: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/5.jpg)
Parameters of Glucose Measurement
![Page 6: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/6.jpg)
SMBG Does Not Give Patients the
Whole Picture
![Page 7: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/7.jpg)
SMBG Does Not Give Patients the
Whole Picture
![Page 8: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/8.jpg)
Glycosylated haemoglobin HbA1c
• Most widely used clinical test
• Measurement of blood glycated haemoglobin(also called haemoglobin A1C,glycohemoglobin and glycosylated haemoglobin [HbA1c], the average amount of A1C
• Changes in a dynamic way
• Reflects the mean blood glucose concentration over the previous six to eight weeks
A1C value of 7% -150mg/dl
A1C value of 9% -210mg/dl
![Page 9: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/9.jpg)
![Page 10: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/10.jpg)
Over past 21 years since the end of
DCCT (1993): The A1c is ..
• Gold Standard for judging level of glycaemic control
• Gold standard for judging risk of DM complications
![Page 11: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/11.jpg)
Mr. BS HbA1c 7
Ms. U HbA1C 7
![Page 12: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/12.jpg)
Does A1C tell the whole story ?
![Page 13: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/13.jpg)
![Page 14: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/14.jpg)
Glycemic variability looking beyond the
HbA1c:
• Even at equal HbA1c, glycemic control can be
extremely different in terms of absolute excursions
Plasma glucose excursions following a meal are generally greater, last longer and are
more variable in patients with type 2 diabetes compared with the normal population
![Page 15: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/15.jpg)
![Page 16: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/16.jpg)
Glycemic variability is a complex phenomenon that includes
both intraday and interday variability
• The intraday component corresponds to the within-day
vertical glycemic fluctuations.
• The interday component is defined as day-to-day
glucose variations
Glycemic Variability
![Page 17: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/17.jpg)
So What Is The Significance of the
Understanding of GV?
♦ “…it suggests that different therapeutic strategies now in use
should be evaluated for their potential to minimize glycemic
excursion, as well as their ability to lower A1c.”
♦ “…wider use of real-time continuous glucose monitoring in clinical
practice would provide the required monitoring tool to minimize
glycemic variability and superoxide overproduction.”
Brownlee M, Hirsch IB: JAMA: 295:1707, 2006
![Page 18: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/18.jpg)
Measures of Glycemic Variability
![Page 19: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/19.jpg)
Reasons of Glycemic Variability
Diminished or absent glycemic auto regulation
OR
Shortfall of insulin availability are hypothesized to be the
etiological factors for these glycemic bumps.
Indian J Endocrinol Metab. 2013 Jul-Aug; 17(4): 611–619
![Page 20: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/20.jpg)
Variations are a Rule
• Glucose variations are not limited to postprandial
hyperglycemic excursions
• Such fluctuations are particularly marked in type 1 diabetes and
to a lesser degree in patients with type 2 diabetes treated with
insulin
• Non-insulin-dependent patients can also experience such peak
and trough patterns with acute glucose variations
• Peaks are usually corresponding to maximum values after
meals particularly mid-morning, while troughs are observed
over inter-prandial periods
![Page 21: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/21.jpg)
Glycaemic Variability- Causes?
• Insulin properties
– Profile of insulin- hexamers to monomers- Zinc/Protamine/pH
– Insulin concentration
– Insulin temperature
– Injection sites
– Depth of injection
• Physician and user factors
– Wrong insulin choices
– Wrong insulin doses
– Erratic lifestyles without flexible regimen / dose adjustments
• Endogenous factors
– SC blood flow
– Age
– Physical exercise
– Obesity
– Hypoglycaemia unawareness?
![Page 22: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/22.jpg)
FACTORS ASSOCIATED WITH GREATER
GLYCEMIC VARIABILITY
• Reduced β cell function
• Older age
• Renal impairment
• Anti-diabetic medication
• Polypharmacy
• Poor compliance with
treatment
• Intake of food with
higher glycemic index
and/or glycemic load
Int J Mol Sci. 2014 Oct; 15(10): 18381–18406.
![Page 23: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/23.jpg)
G.V. Leads to
Vascular Complication
How?
![Page 24: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/24.jpg)
Mechanism by Which Glycemic Variability
LEADS to Complications
• Glycemic variability causes Diabetic Vascular
Complications by two mechanisms:
– Excessive protein glycation end products
– Activation of oxidative stress in the causation of vascular
complication
![Page 25: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/25.jpg)
Growing Evidence
![Page 26: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/26.jpg)
Possible Mechanism
• Human umbilical vein endothelial cells (HUVECs)
“exposed to intermittent hyperglycemia results in ROS
overproduction, through a PKC-dependent
activation …”
• This suggests that glucose fluctuation may be involved
in the development of oxidative stress and vascular
injury
![Page 27: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/27.jpg)
Why This Study Is So Important
• Type 2 diabetes
– Oxidative stress not related to A1C, fasting glucose, fasting
insulin, mean blood glucose
– Stronger correlation of oxidative stress to MAGE than to
postprandial glucose levels
– MAGE = both the ups and the downs of blood glucose
![Page 28: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/28.jpg)
Measuring Oxidative Stress
• Nitrotyrosine: marker for peroxynitrite, a powerful oxidant
increased with hyperglycemia
• 8-hydroxydeoxyguanosine (8-OHdG): a sensitive indicator
of oxidative damage to DNA
• Reactive oxygen species generation by leukocytes
• “A1C of oxidative stress”
• Urinary isoprostanes: best marker of oxidative stress in
total body
• Urinary 8-iso-PGF2-alpha: most common isoprostane
![Page 29: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/29.jpg)
PKCX osm con ox stress X
29
Oxidative Stress Marker Measurements
Nitrotyrosine (7 days)
0
0.1
0.2
0.3
0.4
0.5
0.6
no inhibitor BIMI-I LY379196 mannitol MnTBAP
(mic
roM
)
L
H
H/L
A
B
80HdG (7 days)
0
10
20
30
40
50
no inhibitor BIMI-I LY379196 mannitol MnTBAP
(ng/m
l)
80HdG (14 days)
0
10
20
30
40
50
60
no inhibitor BIMI-I LY379196 mannitol MnTBAP
(ng/m
l)
C
D
Quagliaro L, et al. Diabetes. 2003;52:2795-2804.
Low Glucose
High Glucose
Alternating
High and Low
Glucose
Low Glucose
High Glucose
Alternating
High and Low
Glucose
Low Glucose
High Glucose
Alternating
High and Low
Glucose
Low Glucose
High Glucose
Alternating
High and Low
Glucose
![Page 30: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/30.jpg)
1200
1000
800
600
400
200
0
0 20 40 60 80 100 120 140 160
Uri
na
ry 8
-SO
-PG
F2
alp
ha
Ex
cre
tio
n R
ate
s
(pg
/mg
cre
ati
nin
e)
MAGE (mg glucose/dL)
R=0.86, p<0.0001
Monnier L, et al. JAMA. 2006;295:1681-1687.
Correlation Between Urinary
8-iso-PGF2 alpha (stress marker) and
MAGE in T2DM
30
![Page 31: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/31.jpg)
![Page 32: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/32.jpg)
Glycemic variability A Link between
Diabetes and Cardiovascular Disease?
• Glycemic variability increases:
– Oxidative Stress leading to endothelial damage
– Dyslipidemia
– Glycated Albumin
– Hypoglycemia
Int J Mol Sci. 2014 Oct; 15(10): 18381–18406.
![Page 33: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/33.jpg)
Glycemic variability: A strong independent predictor of mortality in critically ill patients
Increments of mean glucose level is subdivided into four quartiles of glycemic
variability. Q1 represents the lowest quartile; Q4 represents the highest quartile.
Crit Care Med 2008 Vol. 36, No. 11
![Page 34: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/34.jpg)
Glucose variability: associated with cognitive impairment
• In 121 patients with type 2 diabetes (mean age 78 years), MAGE was associated with cognitive impairment independently of HbA1c, FPG and PPG
Rizzo et al. Diabetes Care 2010;33:2169–74
MMSE, mini-mental state examination; PPG, postprandial plasma glucose
20 40 60 80 100
23
24
25
26
27
28
29
MM
SE s
core
r=0.83 p<0.001
MAGE (mg/dL)
20 40 60 80 100
120
-1.5
-1.0
-0.5
0.0
0.5
1.0
1.5
Com
posite s
core
r=0.68 p<0.001
MAGE (mg/dL)
120
![Page 35: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/35.jpg)
Glucose Fluctuations & CVD
• Higher glucose variability is associated with
increased lipid and decreased fibrous contents
with larger plaque burden
• Suggesting glycemic variability as one of the
important factors related to coronary plaque
vulnerability.
J Am Coll Cardiol. 2013;62(18_S1):B195-B195
![Page 36: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/36.jpg)
MAGE & CVD
DIABETES CARE, VOLUME 36, APRIL 2013
![Page 37: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/37.jpg)
Glucose Variability & CAD
Cardiovascular Diabetology 2011, 10:19
![Page 38: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/38.jpg)
GLYCEMIC VARIABILITY IS THE PREDICTOR
OF HYPOGLYCEMIA
Diabetes May 2013 vol. 62no. 5 1405-1408
![Page 39: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/39.jpg)
![Page 40: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/40.jpg)
![Page 41: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/41.jpg)
Hypoglycemia in T1DM & T2DM
• With regard to prediction of hypoglycemia, glucose
variability has been shown predictive of severe
hypoglycemia in T1DM and of non severe
hypoglycemia in T2DM
Diabetes. 2013 May; 62(5): 1405–1408.
![Page 42: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/42.jpg)
Hypoglycemia Increases Cytokines
42
Dostson S, et al. Diabetes Care. 2008;31:1222-1223.
Hypoglycemia
Hyperglycemia
![Page 43: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/43.jpg)
Hypoglycemia is dangerous
Review article, 2013, vol:17(5), pg: 819
![Page 44: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/44.jpg)
Glucose Thermometer
![Page 45: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/45.jpg)
![Page 46: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/46.jpg)
![Page 47: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/47.jpg)
Ambulatory Glucose Profile
(AGP) Decoding Dysglycemia
![Page 48: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/48.jpg)
CGM Indications
![Page 49: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/49.jpg)
• Evaluation of drugs – predicts complications LOS
and mortality
CGM Indications contd.
![Page 50: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/50.jpg)
CGM Limitations
• Technology that cant be used to dose insulin
• All dosing decisions should be based on SMBG
• No replacement for glucose meter
• Not a Device to put and forgotten
– Studies have shown a correlation between the number of
times you look at the receiver and greater reduction in A1c
• Syste that does ’t repla e su stitute for already
existing diabetes management tools
![Page 51: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/51.jpg)
CGM Supports Patients in Proactive vs.
Reactive Self-Management
![Page 52: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/52.jpg)
![Page 53: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/53.jpg)
![Page 54: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/54.jpg)
Recommended use
Age approved
Real time vs. blinded
Dexcom 7 Plus
7 day
18
RT
Dexcom G4
7 day
18
RT
LibrePro
14 day
18
Blinded
MM Guardian
3 day
7
RT or blinded
MM IPro
3 day
7
Blinded
CGM Comparisons
![Page 55: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/55.jpg)
Our Experience of AMBG
Age and Sex Distribution
Age (years) Male Female
20- 35 2 5
36-51 5 2
52-67 7 8
68-83 6 0
Hba1c 6.4% to 12.4%
Total number of patients = 35 (34 patient Type 2 DM and 1
patient Type 1 DM)
![Page 56: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/56.jpg)
Use of AMBG in 35 Patients
1. Evaluate glycemic variability
2. Assess periods of hypoglycemia and hypoglycemia
unawareness
3. Therapeutic and lifestyle interventions
4. Highlighting variability – a major risk factor – normal HbA1c
![Page 57: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/57.jpg)
Ms. K (Type 1 DM) Age 18 years HbA1c 10.8
![Page 58: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/58.jpg)
Ms. K
![Page 59: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/59.jpg)
Ms. K
![Page 60: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/60.jpg)
Ms. K
![Page 61: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/61.jpg)
Mr. AK HbA1c 11 with medication changed to 6.4
![Page 62: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/62.jpg)
Mr. P Poor controlled diabetes
![Page 63: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/63.jpg)
Mr. P
Increase in dosage of medicine and lifestyle measures
![Page 64: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/64.jpg)
Mr. P
![Page 65: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/65.jpg)
AGP is a visual report that collapses all glucose readings from several days or weeks as
if they occurred in a single 24-hour period making it easier to visualize glycemic
patterns*.
65
Rationale for AGP
* Mazze RS. Making sense of glucose monitoring technologies from SMBG to CGM. Diabetes Technology and Therapeutics 2005;7(5):784-7
AGP graph is built from glucose readings, ideally 14 days.
![Page 66: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/66.jpg)
66
The AGP 14-day Profile AGP graphs contain five curves
Median
25th and 75th
Percentile Curves 10th and 90th
Percentile Curves
Median curve (50th percentile) shows the median glucose value for every time point.
The IQR shows the daily, nightly and post-prandial span of 50% of glucose values
Glucose variability exists when glucose values are widely spread, as indicated when
the IQR and 10th and 90th percentile curves cover a large area.
![Page 67: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/67.jpg)
• The 14-day AGP graph clearly shows patterns in glucose levels which enables HCPs to more quickly detect potential problems, such as hypoglycemia and glucose variability.
• The AGP graphs provide the information that HCPs need to assess and fine tune therapy.
67
The key benefits of the 14-day AGP graph
For HCPs and Patients
• The information in the AGP graph is presented in a simplified way that makes it makes it easy to understand.
• The AGP graph provides a link between day-to-day behavior and glucose levels.
Benefits for HCPs
Benefits for Patients
![Page 68: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/68.jpg)
![Page 69: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/69.jpg)
CONCLUSION • Glucose variability indicators describe the glucose profile of diabetic
patients and identify any worsening glycemic control (typical of long
standing diabetes) more accurately than HbA1c.
• Glucose variability is a better predictor for hypoglycaemia compared
with HbA1c.
• Glucose variability is associated with oxidative stress, cognitive
impairment and long-term diabetes outcomes.
• Targeting glycemic variability may help the management
of diabetes better than HbA1c.
• A novel and useful parameter to predict diabetic complications, such
as vascular, hyper/hypoglycemia, in diabetic population.
![Page 70: Dr. Yash Pal Munjal - Welcome to APIDSC · PDF fileDr. Yash Pal Munjal MD, FICP, MAMS, FRCP (EDIN), FACP (USA) FIACM, FIAMS, FIMSA Served API as Past President, Past Dean Editor in](https://reader031.vdocuments.us/reader031/viewer/2022022422/5a9668717f8b9ad96f8cdc91/html5/thumbnails/70.jpg)