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Diabetesand
Cardiovascular disease
Dr. Mashfiqul HasanMD Phase B resident
Department of EndocrinologyBangabandhu Sheikh Mujib Medical University
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Agenda
1. CV risk in DM
2. CV risk management in DM
3. DM management in CVD
4. DM management in acute setting
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1. CV risk in DM
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Huge and growing problem
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Diabetes
Is considered as
Cardio-vascular risk
equivalent
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Insulin resistance is linked to a range of CVD risk factors
Insulin resistance
Dyslipidaemia
Microalbuminuria
CVD
Vascular
inflammationHypertension
Atherosclerosis
Endothelial
dysfunction
Adapted from McFarlane SI, et al. J Clin Endocrinol Metab 2001;86:713–718.
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Problem 1
• Stratify according to CVD risk
(highest to lowest)
A. Prior MI, no DM
B. DM, no prior MI
C. No DM, no prior MI
D. Both DM and prior MI
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2. CV risk management in DM
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Major focus
Comprehensive CV risk reduction
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Treat
cardiovascular risk factors
in diabetic patients
as aggressively as
in non-diabetic patients
with prior myocardial infarction
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Blood pressure
• <140/90 mm of Hg in general
• <130/80 mm of Hg if possible
• Lifestyle therapy
• Pharmacological therapy
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Dyslipidemia
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Anti-platelet agent
• Secondary prevention
• Primary prevention
– Men >50 yr, Women >60 yr
– Additional CV risk factors
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Smoking cessation
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DECODE: IGT Increases Mortality Risk
Diabetes Epidemiology: Collaborative analysis Of Diagnostic criteria in Europe
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mashfiq-endocrinology-bsmmu 20
Problem-2
• A 56-year-old man with T2DM
• Taking OAD, HbA1C 7.2
• BMI 31.1 kg/m2
• No history of CVD, BP 145/95, non-smoker
• Q. Does he need statin therapy?
• Q. Does he need anti-platelet therapy?
• Q. What is the choice of antihypertensive?
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3. DM management in CVD
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Impact of Intensive Therapy for Diabetes: Summary of Major Clinical Trials
Study Microvasc CVD Mortality
UKPDS
DCCT / EDIC*
ACCORD
ADVANCE
VADT
Long Term Follow-up
Initial Trial
* in T1DM23mashfiq-endocrinology-bsmmu
- HbA1c < 7.0%
- Pre-prandial 4.4-7.2 mmol/l)
- Post-prandial <10.0 mmol/l
- Individualization is key:
Tighter targets (6.0 - 6.5%) - younger, healthier
Looser targets (7.5 - 8.0%) - older, comorbidities, hypoglycemia prone, etc.
- Avoidance of hypoglycemia
Glycemic targets
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more stringent
less stringent
Patient attitude and expected treatment efforts highly motivated, adherent,
excellent self-care capacities
less motivated, non-adherent,
poor self-care capacities
Risks potentially associated with hypoglycemia and other drug adverse effects
low high
Disease duration newly diagnosed long-standing
Life expectancy long short
Important comorbidities absent severe few / mild
Established vascular complications absent severe few / mild
Readily available limited
Usually not modifiable
Potentially modifiable
HbA1c7%
PATIENT / DISEASE FEATURES
Approach to the management of hyperglycemia
Resources and support system
Figure1.Modula onoftheintensivenessofglucoseloweringtherapyinT2DM
Diabetes Care 2015;38:140-149; Diabetologia 2015;10.1077/s00125-014-3460-0
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Healthy eating, weight control, increased physical activity & diabetes education
Metformin high low risk
neutral/loss
GI / lactic acidosis
low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors):
Metformin +
Metformin +
Metformin +
Metformin +
Metformin +
high low risk
gain
edema, HF, fxs
low
Thiazolidine- dione
intermediate low risk
neutral
rare
high
DPP-4 inhibitor
highest high risk
gain
hypoglycemia
variable
Insulin (basal)
Metformin +
Metformin +
Metformin +
Metformin +
Metformin +
Basal Insulin +
Sulfonylurea
+
TZD
DPP-4-i
GLP-1-RA
Insulin§
or
or
or
or
Thiazolidine-dione
+ SU
DPP-4-i
GLP-1-RA
Insulin§
TZD
DPP-4-i
GLP-1-RA
high low risk
loss
GI
high
GLP-1 receptor agonist
Sulfonylurea
high moderate risk
gain
hypoglycemia
low
SGLT2 inhibitor
intermediate low risk
loss
GU, dehydration
high
SU
TZD
Insulin§
GLP-1 receptor agonist
+
SGLT-2 Inhibitor +
SU
TZD
Insulin§
Metformin +
Metformin +
or
or
or
or
SGLT2-i
or
or
or
SGLT2-i
Mono- therapy
Efficacy* Hypo risk
Weight
Side effects
Costs
Dual therapy†
Efficacy* Hypo risk
Weight
Side effects
Costs
Triple therapy
or
or
DPP-4 Inhibitor
+ SU
TZD
Insulin§
SGLT2-i
or
or
or
SGLT2-i
or
DPP-4-i
If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors):
If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:
Metformin +
Combination injectable therapy‡
GLP-1-RA Mealtime Insulin
Insulin (basal)
+
or
or
or
Diabetes Care 2015;38:140-149; Diabetologia 2015;10.1077/s00125-014-3460-0
Figure2B.An -hyperglycemictherapyinT2DM:Avoidanceofweightgain
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Adapted Recommendations: When Goal is to Avoid HypoglycemiaDiabetes Care, Diabetologia. 19 April 2012
[Epub ahead of print]
ADA-EASD Position Statement: Management of
Hyperglycemia in T2DM
4. OTHER CONSIDERATIONS
• Comorbidities
- Coronary Disease
- Heart Failure
- Renal disease
- Liver dysfunction
- Hypoglycemia
Metformin: CVD benefit (UKPDS)
Avoid hypoglycemia
? SUs & ischemic preconditioning
? Pioglitazone & CVD events
? Effects of incretin-based therapies
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]29mashfiq-endocrinology-bsmmu
ADA-EASD Position Statement: Management of
Hyperglycemia in T2DM
4. OTHER CONSIDERATIONS
• Comorbidities
- Coronary Disease
- Heart Failure
- Renal disease
- Liver dysfunction
- Hypoglycemia
Metformin: May use unless condition is unstable or severe
Avoid TZDs
? Effects of incretin-based therapies
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]30mashfiq-endocrinology-bsmmu
ADA-EASD Position Statement: Management of
Hyperglycemia in T2DM
4. OTHER CONSIDERATIONS
• Comorbidities
- Coronary Disease
- Heart Failure
- Renal disease
- Liver dysfunction
- Hypoglycemia
Increased risk of hypoglycemia
Metformin & lactic acidosis
US: stop @SCr ≥ 1.5 (1.4 women)
UK: dose @GFR <45 & stop @GFR <30
Caution with SUs (esp. glyburide)
DPP-4-i’s – dose adjust for most
Avoid exenatide if GFR <30Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
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ADA-EASD Position Statement: Management of
Hyperglycemia in T2DM
4. OTHER CONSIDERATIONS
• Comorbidities
- Coronary Disease
- Heart Failure
- Renal disease
- Liver dysfunction
- Hypoglycemia
Most drugs not tested in advanced liver disease
Pioglitazone may help steatosis
Insulin best option if disease severe
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]32mashfiq-endocrinology-bsmmu
ADA-EASD Position Statement: Management of
Hyperglycemia in T2DM
4. OTHER CONSIDERATIONS
• Comorbidities
- Coronary Disease
- Heart Failure
- Renal disease
- Liver dysfunction
- Hypoglycemia Emerging concerns regarding
association with increased
mortality
Proper drug selection in the hypoglycemia prone
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]33mashfiq-endocrinology-bsmmu
Long (Detemir)
Rapid (Lispro, Aspart, Glulisine)
Hours
Long (Glargine)
0 2 4 6 8 10 12 14 16 18 20 22 24
Short (Regular)
Hours after injection
Insu
lin le
vel
(Degludec)
• Therapeutic options: Insulins
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4. DM management in acute setting
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Sliding scale insulin (SSI)
in the inpatient hospital setting
Strongly discouraged
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Critically ill patients
• Insulin therapy should be initiated for treatment of persistent hyperglycemia
• starting at a threshold of no greater than
10 mmol/L
• Once insulin therapy is started, a glucose range of 7.8–10 mmol/L is recommended for the majority of critically ill patients
mashfiq-endocrinology-bsmmu 37
Non-critically ill patients
• If treated with insulin, generally premealblood glucose targets of 7.8 mmol/L with random blood glucose 10.0 mmol/L are reasonable
• A basal plus correction insulin regimen is the preferred treatment for patients with poor oral intake
mashfiq-endocrinology-bsmmu 38
Insulin aspart is a rapid acting insulin analogue. Brand name is NovoRapid®.
Where B 28 position amino acid proline is replaced by aspartic acid through recombinant DNA technology.
Fig: Structure of Insulin aspart
What is insulin aspart?
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Kinetics-Dynamics
Human Actrapid ®
30 mins
1.5 -3.5 hours
7-8 hours
NovoRapid ®
10-20 minutes
1-3 hours
3-5 hours
Onset of action
Peak action
Duration of action
NovoRapid ® has a faster onset , earlier peak and sharp return to baseline
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Heinemann L et al. Diabet Med 1996;13:683
Insulin aspart has a faster onset, earlier peak and sharp return to baseline
Insulin aspart (NovoRapid®)
Human Actrapid ®
(0.2 U/kg)
Time (minutes)
Se
rum
in
su
lin
(pmol/l)(mU/l)
50
25
75
500
400
300
200
100
0
0 60 120 180 240 300 360 420 480 540 600-60
0
48 min/ 414 pmol/l
123 min/ 239 pmol/l
Doubleblind, cross-over, single dose study in healthy volunteers, N=24
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Reduces risk of hypoglycemia
0
0.2
0.4
0.6
0.8
1
1.2
1.4
Total Nocturnal 24:00 – 6:00
Ep
iso
des p
er
pati
en
t p
er
year
NovoRapid ®
Human Actrapid ®
***
Heller et al. Diabetes 2001;50(2):A137
72%
4 months
*** p < 0.005
NovoRapid® reduces the rate of severe nocturnal hypoglycaemia by 72%
Double-blind, crossover comparison in T1DM on basal-bolus, Duration 4 mo, N=155
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• Improves long term glucose control– Significantly improved and maintained stable HbA1c levels
over 3 yr compared to Actrapid ® (Amiel S et al, 2001)
• Reduces risk of hypoglycemia– Only analogue to show a 72% reduction in severe hypo
(Heller S et al, 2001)– Rapid onset, short duration, sharp return to baseline
(Heinemann L et al, 2001)
• Freedom from meal-time constraints– Ideal for children and adults with unpredictable meal size– Offers option of dose adjustment based on meal-size
(Danne T et al, 2003)
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Slide no 44
IV use of Insulin aspart in Hospitalized patients
Pre operative Pre ICU or Pre admission
S.C. NovoRapid
During Surgery, ICU or Hospitalization
IV NovoRapid
After surgery Shift to ward Just before discharge
S.C. NovoRapid
Same insulin; predictable control; better SC insulin; less loss
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Acknowledgements
• Prof. Md. Fariduddin
• Prof. M A Hasanat
• Novo Nordisk
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Thank you
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Questions?
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