Insulin Therapy In The Treatment Of T2DM Prof. Ibrahim El-Ebrashy Cairo University Head Of Diabetes...
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Insulin TherapyIn The Treatment Of T2DM
Prof.
Ibrahim El-EbrashyCairo University
Head Of Diabetes & Endocrinology Center
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T2DM is insulin resistance + insulin deficiency
Type 2 diabetes
– Characterised by insulin resistance and insulin deficiency
– Degrees of resistance and deficiency vary but insulin deficiency is key to developing diabetes
Adapted from Bergenstal et al. In: Degroot & Jameson (eds). Endocrinology 2001;821–35
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Slide No 3
Natural history: insulin secretion and blood glucose control
IFG, impaired fasting glucose
35030025020015010050
Postprandial glucose
Fasting glucose
Obesity IFG Diabetes Uncontrolled hyperglycaemia
250200
15010050
Insulin resistance
Insulin level
Years of diabetes
–10 2520151050–5 30
Beta-cell failure
Glu
cose level
(mg
/dL)
Rela
tive
fun
cti
on
(%
)
Normal
Normal
Adapted from Bergenstal et al. In: Degroot & Jameson (eds). Endocrinology 2001;821–35
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Improving control reduces risks of long-term complications
• Every 1% drop in HbA1c can reduce long-term diabetes complications
43%
Lower extremity amputation or fatal peripheral
vascular disease
37%
Microvascular disease
19%
Cataract extraction
14%
Myocardial infarction
16%
Heart failure
12%
Stroke
UKPDS 35: Stratton et al. BMJ 2000;321:405–12
Slide no 4
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Positive legacy effect of early, intensive glucose control
RRR = Relative Risk Reduction
Red indicates significant reduction on intensive therapy vs. conventional therapy
At end of post-trial follow up (median 8.5 years)
Aggregate endpoint 1997 2007
Any diabetes-related endpoint
RRR: 12% 9%
Microvascular disease RRR: 25% 24%
Myocardial infarction RRR: 16% 15%
All-cause mortality RRR: 6% 13%
UKPDS 80. Holman et al. N Engl J Med 2008; 359:1577-89
Slide no 5
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Insulin is the most effective anti-diabetic agent
Nathan DM. N Engl J Med. 2007;356:437-40
Slide no 6
1.5 1.5 1.0-1.5 0.5-0.9 0.8-1.0
≥2.5
SulfonylureasBiguanides(metformin) Glinides
DPP-IVinhibitors TZDs Insulin
0.0
0.5
1.0
1.5
2.0
2.5
3.0
HbA
1c re
duct
ion (
%)
Efficacy as mono
therapy
Anti diabetic agents
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Insulin use is often delayed, despite poor glycaemic control
Slide no 7
1 OAD
2 OADs
3 OADs
Diet
2.9 years 4.7 years 2.5 years 2.7 years
8
9
10
8.8%
9.4% 9.1%
OAD, oral antidiabetic drug
Mean H
bA
1c a
t la
st
vis
it (%
)
Novo Nordisk. Type 2 Diabetes Market Research Roper Starch US Study, 2000
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T2DM treatment patterns in Egypt2010-14, thousand patients
Slide no 9
2010-12Change
16%
11%
11%
3%
16%
100%
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There is resistance to insulin despite efficacy and guideline recommendations
In a survey of insulin-naïve T2DM patients, 28.2% of respondents reported that they would be unwilling to take
insulin if it were prescribed3
UKPDS• 27% of T2DM patients randomized to insulin
initially refused treatment1
DAWN• More than half of insulin-naïve T2DM patients
expressed anxiety about starting insulin therapy2
1UKPDS 33, 1998; 2Peyrot et al. 2005; 3Polonsky et al. 2005Kunt and Snoek Int J Clin Pract 2009; 63:6-10
Slide no 10
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Barriers to starting insulin• Fear of hypoglycaemia
• Fear of reduced quality of life
• Reluctance to inject in public
• Perception that the disease is becoming more severe
• Fear of needles/pain from injections
• Patients do not feel empowered to take control of their diabetes
Korytkowski . Int J Obes Relat Metab Disord 2002;26:S18–S24Polonsky et al. Diabetes Care 2005;28(10):2543-2545
Rubin and Peyrot. J Clin Psychol 2001;57:457– 478
Slide no 11
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Clinical inertia: delay in treatment initiation and optimisation
TherapyTherapyN=66726N=66726
Diabetes durationDiabetes duration(years)(years)
Mean (SD)Mean (SD)
HbAHbA1c 1c
(%)(%)Mean (SD)Mean (SD)
No therapy
(9%)2.1 (8.6) 10.0 (2.2)
OGLD only
(58%)8.3 (6.3) 9.5 (1.7)
Insulin +/- OGLD
(33%)12.0 (7.7) 9.4 (1.8)
Home et al. Diabetes Res Clin Pract 2011; 94: 352-63
Slide no 13
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Often there is a failure to advance therapy even when required
Time to insulin initiation in patients on >1 OAD is 7.7 yrs†
Perc
enta
ge P
ati
ents
(%
)
Delay in insulin initiation (years)
†95% CI = 7.4 to 8.5 years
Calvert et al. Br J Gen Pract 2007;57:455-460
Slide no 14
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Common reasons for clinical inertia
Insulin makes one fat
Fear ofhypos
Pain frominjection
Pain fromblood tests
Insulin makes one fat
Fear ofhypos
Pain frominjection
Pain fromblood tests
* Percentage of patients/physicians interviewed who provided this as a reason for not starting insulin
Insulin naïve patients Primary care physicians
Nakar et al. J Diabetes Complications 2007;21:220–6
Slide no 15
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Patient concerns still exist after insulin initiation
0
10
20
30
40
50
60
70
80
Diabeteshas
progressed
Lessflexibility
Injectionfear
Weightgain
Seen as sick
p<0.001 for all
Perc
en
tag
e o
f su
bje
cts
wh
o a
gre
eor
str
on
gly
ag
ree
Insulin naïve
Insulin-treated
Increased risk ofhypoglycaemia
Snoek et al. Health and Quality of Life Outcomes 2007;5:69
Slide no 16
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Sequential Insulin Strategies in T2DM Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
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Algorithm for initiating insulin therapy.
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Patient-Based Insulin Regimens
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Starting Dosages Start Low and Titrate Steadily
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Dosage Titration for Once-Daily or Twice-Daily Insulin Regimens
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Transition From One Regimen to Another
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Data about Premixed Insulin Aspart in treatment of Diabetes
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Nazia Raja-Khan, Sarah S Warehime, and Robert A Gabbay
Vasc Health Risk Manag. 2007 December; 3(6): 919–935.
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Percentage of subjects achieving HbA1c target values at the end of the study.
Raskin P et al. Dia Care 2005;28:260-265
Copyright © 2011 American Diabetes Association, Inc.
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Eight-point SMPG readings before breakfast, lunch, and supper [BB, BL, and BD] and 90 min after breakfast, lunch, and supper [B90, L90, and D90]; at bedtime [Bed]; and at 3:00 a.m.).
Raskin P et al. Dia Care 2005;28:260-265
Copyright © 2011 American Diabetes Association, Inc.
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Case 1
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q A 49-years-old male patient with T2DM 8 years ago, being treated with Insulin Glargine 20 unites at 11 pm and glimpride 3mg before breakfast and metformin 2g/day since 2 years
BMI 30
qLifestyle:
High-carbohydrate meals is fond of rice or bread and potatoes.
Does not exercise.
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•HbA1c = 7.5%
•On antihypertensive for several years.
•Recently, a statin has been added to his
medications
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He wants to fast in ramadan?
Yes
No
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• What due think you should first ask before deciding the his treatment regimen in ramadan ?
1. His blood glucose analysis during the day
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• Blood glucose levels over the day:
FBG 145mg/dl
PPG (Post-breakfast) 165 mg/dl
Pre Lunch 133 mg/dl
PPG (Post-Lunch) 167 mg/dl
Pre Dinner 166 mg/dl
After Dinner ( main meal ) 261 mg/dl
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What are the option to control his blood glucose ?
• Increase the dose of glargine?
• Add a mealtime bolus?
• Shift to basal-bolus insulin regimen?
• Switched to premixed analogue insulin before eftar and SU at a lower dose before sohoor and the same metformin doses?
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• What dietary advice you have to give him in Ramadan ?
1. Eftar starting with a lot of fluids and no sugar
2. Snack after praying taraweeh
3. Lot of fluid during the time allowed to eat
4. Late sohoor
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Thank You