3. It is also considered as a worldwide
epidemic and one of the most common
chronic diseases in both developed and
CAD accounts for as many as 80% of deaths
among individuals with DM compared
with 30% in those without DM.
5. The prevalence of T2DM which correlates
closely with obesity has shown a sharp rise
over recent decades. Consequently the
management of DM & other CAD risk factors is
the main focus in the primary and secondary
prevention of cardiovascular events.
6. Diabetes is a huge and growing problem, and the costs to
society are high and escalating
382 million people have
By 2035, this number will
rise to 592 million
IDF ,Global burden of
diabetes , 2013
9. The pathological continuumThe pathological continuum
Normal glucose tolerance
Impaired fasting glucose
Impaired glucose tolerance
10. Impact of diabetes on CVD:Impact of diabetes on CVD:
Both T1DM and T2DM confer significantly
elevated risks (2-5 folds) of:
CAD, ACS, post MI complications.
Sudden cardiac death.
End stage renal failure.
12. Diabetes as a CHD Risk Equivalent:Diabetes as a CHD Risk Equivalent:
Type 2 DM and CHDType 2 DM and CHD
7-Year Incidence of Fatal/Nonfatal MI7-Year Incidence of Fatal/Nonfatal MI
(East West Study)(East West Study)
No Diabetes Diabetes
CHD=coronary heart disease; MI=myocardial infarction; DM=diabetes mellitus
Haffner SM et al. N Engl J Med. 1998;339:229-234.
13. In the Framingham Heart Study, the risk of
CAD is doubled in men and tripled in women
with diabetes, compared with age-matched
subjects without diabetes.
Patients with diabetes present differently from
those without diabetes and are much more
likely to experience an acute coronary
syndrome without chest pain known as “silent
14. Indeed, there are multiple studies
suggesting poorer outcomes following
cardiovascular events, even with
revascularization, for individuals with
diabetes compared with those without.
Cardiogenic shock is more common and
more severe in post-MI patients with
15. Risk factors for CAD in patients
The risk factors that predispose individuals
with diabetes to develop cardiovascular
disease are the same as those that raise
cardiovascular risks in those without
However, the prevalence of known major
risk factors for CAD is generally amplified
among persons with diabetes.
This is one of the most profound risk factors
among individuals with diabetes.
Diabetes is associated with:
Small, dense low-density lipoprotein (LDL)
Increased levels of apolipoprotein B and E.
Low levels of high-density lipoprotein (HDL)
High triglyceride (TG) levels.
20. Lipid-lowering therapy is now a
cornerstone of T2DM management.
In the Scandinavian Simvastatin Survival
Study (4S4S), there was a 55% reduction in
cardiovascular events among subjects with
diabetes, a 25% reduction in the CARECARE trial
and 24% reduction in the LIPIDLIPID trial with
21. In the Collaborative AtoRvastatin Diabetes
Study (CARDSCARDS), atorvastatin 10 mg reduced
LDL-C by 40% on average. Results at 4 years
showed a 37% relative risk reduction (p
<0.001) in the primary endpoint & 27%
relative risk reduction in the secondary
Elevated fasting TG levels are characteristic
of the lipid panel in diabetes and constitute
an independent cardiovascular risk factor.
Hypertriglyceridemia correlates with
Fibrates have traditionally been considered
an appropriate therapy to target
hypertriglyceridemia and have often been
added to statin therapy for this indication.
The prevalence of hypertension is increased
in individuals with diabetes compared with
In the UKPDS, lowering the blood pressure
to a mean of 144/82 mm Hg (compared with
154/87 mm Hg) significantly reduced
strokes, diabetes related deaths, and heart
failure, as well as microvascular
24. Several trials have demonstrated the renal
protective effects of angiotensin-converting
enzyme inhibitors (ACEIs) or angiotensin
receptor antagonists (ARBs) over alternate
agents, which has firmly established them as
the first-line antihypertensives in diabetes.
There is currently insufficient evidence to
recommend ACE inhibitors in normotensive
patients with diabetes without
25. Major guidelines suggest a target blood
pressure in patients with diabetes of < 130/80
The ACCORD trial randomized subjects with
diabetes to a target systolic blood pressure of <
120 mmHg or < 140 mmHg. The lower target
group showed no difference in the primary
cardiovascular outcomes end point but did
have a significantly lower stroke rate; however,
this was at the expense of significantly more
adverse drug events and an increased risk of a
creatinine rise of> 1.5 mg/dL.
Obesity and overweight are typically
defined in terms of body mass index (BMI),
Overweight being 25 to 30 kg/m2
Class I obesity 30 to 35 kg/m2
Class II obesity 35 to 40 kg/m2
Class III obesity > 40 kg/m2
28. Waist circumference and waist-to-hip ratio
better reflect abdominal adiposity and are
more reliable predictors of CAD outcomes
T2DM correlates closely with obesity,
especially central obesity.
Caloric restriction, behavior modification,
and increased physical activity form the
basis of weight management programs.
29. Drugs for weight loss:
Ephedrine and ephedra alkaloids
Phentermine and diethylpropion
Orlistat (pancreatic lipase inhibitor)
Others (antidepressants such as fluoxetine,
sertraline, bupropion & anti-epileptics such as
topiramate and zonisamide; and diabetes
including metformin and the glucagon like
peptide (GLP) analogs).
30. There is growing evidence regarding the
beneficial effects of significant weight loss
achieved by bariatric surgery on glucose
Bariatric surgery is generally restricted to
individuals with BMI >40 kg/m2
or BMI 35
to 40 kg/m2
with co-existing medical
conditions such as diabetes.
31. Bariatric surgery options include :
Malabsorptive procedures such as the
Roux-en-Y gastric bypass.
Restrictive procedures such as
laparoscopic adjustable gastric bands and
34. Role of DM in the pathology ofRole of DM in the pathology of
Diabetes accelerates the atherosclerosis
process & endothelial dysfunction.
Autopsy series have revealed more diffuse
coronary involvement, greater severity of
vessel stenosis, and more severe left main
disease in persons with diabetes, compared
with those without.
35. NONO is among several key substances that
maintain healthy endothelial function,
which includes freedom from adhesion
molecule activation, leukocyte diapedesis,
platelet aggregation, and activation of
36. Current research reveals the impact of
excessive oxidative stress (which can he
induced by hyperglycemia, fatty acids, or
insulin resistance) on NONO production and
also on the generation of advanced glycation
end products (AGEPsAGEPs), which are suspected
to mediate various negative cellular effects
Reactive oxygen substances (ROS).
Hyperglycemia : NO by:
Its degradation by formation of ROS
through protein kinase C, NADPH oxidases
and AEGs (Advanced End Glycation
40. Platelet function is also abnormal in
diabetes, with overexpression of the
glycoprotein IIb/IIIa receptor promoting
inappropriate platelet adhesion and
Endothelin-1 , Angiotensin II &
prostanoids , V.C. response to
catecholamines (autonomic dusfunctionautonomic dusfunction).
43. MICROVASCULAR TRIALSMICROVASCULAR TRIALS
The role of tight control of glycemia was
firmly established in the 1990s with the
publication of two large trials demonstrating
decreases in microvascular complications
nephropathy and retinopathy with lower
44. In summary,
The two large trials published in the 1990s,
DCCT and UKPDS,DCCT and UKPDS, showed significant
improvements in microvascular outcomes
with tighter glycemic control in T1DM or
45. MACROVASCULAR TRIALSMACROVASCULAR TRIALS
Despite the convincing evidence for a
reduction in microvascular complications,
the relationship between glycemia and
cardiovascular events remained unclear,
with neither DCCT nor UKPDS showing a
definitive advantage in terms of
cardiovascular outcomes or mortality.
46. Three further large trials added additional
information regarding the potential
relationship between glycemic control and
47. The ADVANCEADVANCE trial (Action in Diabetes and
Vascular Disease: Preterax and Diamicron Modified
Release Controlled Evaluation) randomized 11,140
patients with T2DM to standard versus
intensive glucose control.
Intensive control was achieved with the use
of gliclazide (a sulfonylurea) plus other
agents as necessary to achieve a HbAlc 6.5%
48. There was a decrease in the incidence of
microvascular events (primarily
macroalburninuria) but no significantno significant effect
of the type of glucose control on major
49. The ACCORD trialThe ACCORD trial (Action to Control
Cardiocascular Risk in Diabetes) also tested the
effects of tight glucose control, recruiting a
total of 10,251 T2DM patients who were
randomized to a target HbAlc of < 6% versus
7.0% to 7.9%
50. ACCORD was discontinued at a meanACCORD was discontinued at a mean
follow-up of 3.5 years due to an increasedfollow-up of 3.5 years due to an increased
risk of death in the intensive treatment arm.risk of death in the intensive treatment arm.
Hypoglycemia requiring medical attention
and weight gain > 10 kg were both more
common in the intensive therapy group.
51. Trials Show No Reduction in CV Events withTrials Show No Reduction in CV Events with
More Intensive Glycemic ControlMore Intensive Glycemic Control
ACCORD Study Group. N Engl J Med. 2008;358:2545-2559.
ADVANCE Collaborative Group. N Engl J Med. 2008;358:2560-2572.
Number at Risk
Intensive 5570 5369 5100 4867 4599 1883
Standard 5569 5342 5065 4808 4545 1921
0 12 24 36 48 60
Months of follow-up
ADVANCE: Primary Outcome
Number at Risk
Intensive 5128 4843 4390 2839 1337 475 448
Standard 5123 4827 4262 2702 1186 440 395
0 1 2 3 4 5 6
ACCORD: Primary Outcome
52. In the VADTVADT (Veterans Affairs Diabetes Trial)
there was no significant difference observed
between the two groups in any component
of the primary outcome or in all-cause
54. The 2009 ACC/AHA Scientific Statement
supports a goal HbA1c of ≤ 7a goal HbA1c of ≤ 7 with
acknowledgment of the benefits of tight
control in terms of microvascular disease,
but recognizes the paucity of evidence for a
55. Diabetic CardiomyopathyDiabetic Cardiomyopathy
One reason for the poor prognosis in
patients with both diabetes and ischemic
heart disease seems to be an enhanced
myocardial dysfunction leading to
accelerated heart failure.
Thus, patients with diabetes are unusually
prone to congestive heart failure.
56. Several factors probably underlie diabetic
Accelerated coronary atherosclerosis.
Chronic hyperglycemia, microvascular
disease, endothelial dysfunction, altered
calcium handling, accumulation of AGEPs
and FFAs, glycosylation of myocardial
proteins, and autonomic neuropathy.
57. Guide toGuide to
Comprehensive RiskComprehensive Risk
Reduction forReduction for
Patients WithPatients With
Coronary and OtherCoronary and Other
Vascular DiseaseVascular Disease
Who Have DiabetesWho Have Diabetes
58. Lifestyle Modifications for primaryLifestyle Modifications for primary
and secondary prevention of CADand secondary prevention of CAD
(JNC VI. Arch Intern Med. 1997)
1- Reduce weight 3-Moderate consumption
• Sodium (6gm/day)
• saturated fat
4-Maintain adequate intake of dietary:
62. Blood pressure controlBlood pressure control
Initiate lifestyle modification, weight
control, physical activity, alcohol and
smoking cessation, and moderate sodium
restriction in all patients with blood
pressure > 130 mm Hg systolic or 85 mm Hg
Goal: ≤ 130/85 mm HgGoal: ≤ 130/85 mm Hg
63. Add blood pressure medication according
to other patient requirements and
characteristics (i.e. age, race, compelling
BP is not < 140 mm Hg systolic or < 90 mm
Hg diastolic in 3 months or if initial BP is >
160 mm Hg systolic or > 100 mm Hg
Type 2 Diabetes and CHD 7-Year Incidence of Fatal/Nonfatal MI (East West Study)
Prior to completion of this study, little data existed to compare mortality rates from coronary heart disease (CHD) in patients with diabetes, but without prior myocardial infarction (MI), and patients without diabetes, but with a history of MI. To sort out the risks among the groups and determine whether patients with diabetes and no MI history should be treated as aggressively for cardiovascular (CV) risk factors as patients who have had an MI, the 7-year incidence MI in 2432 patients (1059 with diabetes, 1373 without diabetes) was quantified.
Results indicate, the 7-year incidence of MI in patients with diabetes was 45.0% for those with a previous MI, and 20.2% for patients without an MI at baseline (P&lt;0.001). Among patients without diabetes, but with a positive history for prior MI, 7-year incidence of MI was 18.8%. Kaplan-Meier estimates that the probability of death from CHD reveals similar outcomes for patients with diabetes/no history of MI and no diabetes/history of MI. The hazard ratio for death from CHD for the 2 groups was not significantly different from 1.0 (hazard ratio, 1.4; 95% confidence interval [CI]) of 0.7 to 2.6). This hazard ratio remained close to 1.0 even after adjustment for total cholesterol, hypertension, and smoking.
These data support that treatment of CV risk factors in patients with diabetes and no history of MI should be as aggressively treated as with patients without diabetes, but with a history of previous MI.
Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229-234.
A key concept of cardiometabolic risk is that the risk factors tend to cluster, as illustrated in this diagram. The cardiovascular and metabolic variables are often associated with each other and therefore can occur simultaneously. In recent years, the clustering of cardiometabolic risk factors has received increasing attention, leading groups such as the World Health Organization, International Diabetes Federation, and the Adult Treatment Panel III (ATP III) (National Cholesterol Education Program) to issue clinical guidelines for identifying this particular group of risk factors as the metabolic syndrome.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497.