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Causes of Death in People with Diabetes
50
40
30
deaths
20
10
0
Ischaemic Heart Disease
Other Heart Disease
Diabetes
Cancer
Stroke
Infection
Other
Geiss LS, et al. In Diabetes in America, 2nd ed.
1995. Bethesda, MD NIH 1995
2
TYPE 2 DIABETES
Hyperglycaemia (Insulin resistance)
Hypertension
Impaired fibrinolysis
Dyslipidaemia
Central obesity
Endothelial dysfunction
Proinflammatory state
Hypertriglycaeridemia
Low HDL-C
Small, dense LDL-C
CVD
3
Relationship Between Glycemic Control and
Coronary Heart Disease Events in Type 2 Diabetes
Patients (Ages 65 to 74)
25
20
HbA1c lt7.0
15
HbA1c ³7.0
3.5-yr Incidence ()
10
5
0
lt6
³6
Duration of Diabetes (yr)
Kuusisto J et al. Diabetes. 199443960-967.
4
Fatal and Non-Fatal Myocardial Infarction
5
Fatal and Non-Fatal Stroke
6
Amputation or Death from Peripheral Vascular
Disease
7
Myocardial Infarction and Microvascular Disease
UKPDS 35. BMJ 2000 321 405-12
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Pharmacologic Management of Type 2 Diabetes

• Insulin Secretagogues
• Sulfonylureas
• Glimepiride
• Glipizide
• Gliclazide
• Glyburide, etc
• Meglitinides
• Repaglinide
• Nateglinide
• Delayed Glucose Absorption
• ?-Glucosidase Inhibitors
• Acarbose
• Voglibose

• Insulin Sensitizers
• Metformin
• Glitazones (Thiazolidinediones)
• Rosiglitazone
• Pioglitazone

• Insulin

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DIGAMI
Randomized patients
G I therapy n 306 (DM1 56 DM2 250)
Standard therapy n 314 (DM1 51 DM2 263)
Glycaemic goal 125-180 mg/dl
9.1 12.4 18.6
Intrahospital mortality (ns) 3 month mortality
(ns) 12 month mortality (plt0,02)
11.1 15.6 26.1
Malmberg et al, JACC 1995
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Intensive insulin therapy in critically ill
patients
Glycaemic goal 80 110 mg/dl (control 180 200
mg/dl)
Van Den Berghe et al. NEJM, 2001
12
Blood Pressure and Risk for Coronary Heart
Disease in Men
Age 65-94
Age 65-94
Age-adjusted annualincidence of CHD per 1000
Age 35-64
Age 35-64
Systolic blood pressure (mmHg)
Diastolic blood pressure (mmHg)
Based on 30 year follow-up of Framingham Heart
Study subjects free of coronary heart disease
(CHD) at baseline
Framingham Heart Study, 30-year Follow-up. NHLBI,
1987.
13
UKPDS Impact of Tight vs Less Tight Blood
Pressure Control on Diabetes-Related Endpoints
n758 (mean achieved blood pressure of 144/82
mmHg) n390 (mean achieved blood pressure of
154/87 mmHg)
0.1
1
10
Favors tightcontrol
Favors less tight control
Adapted from UKPDS Group. BMJ. 1998317703713.
14
MICRO-HOPE Events Per Patient Group for Primary
Endpoint and Components
RR25 Plt0.001
RR22 P0.01
RR37 Plt0.001
Events per patient group ()
RR33 P0.007
Combined primary endpoint
Myocardial infarction
Stroke
Cardiovascular death
The occurrence of myocardial infarction, stroke
or cardiovascular death
RRRelative risk reduction
HOPE Study Investigators. Lancet.
2000355253-259.
15
Relative Risk Reduction With ACEIs in ABCD,
CAPPP and FACET
Acute Myocardial Infarction
Cardiovascular Event
All-cause Mortality
Stroke
NS
relative risk reduction
P0.01
Plt0.001
Plt0.001
Pahor M, et al. Diabetes Care. 200023888-892.
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IDNT Irbesartan vs Amlodipine Primary and
Secondary Endpoints
Composite of a doubling of serum creatinine, end
stage renal disease, or death Composite of death
from cardiovascular causes, nonfatal myocardial
infarction, heart failure resulting in
hospitalization, a permanent neurologic deficit
caused by a cerebrovascular event, or lower limb
amputation above the ankle
Lewis EJ, et al. N Engl J Med. 2001345(12)851-86
0.
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2003 European Society of Hypertension European
Society of Cardiology guidelines for the
management of arterial hypertension Antihypertensi
ve therapy in diabetics
1. The goal blood pressure to aim at during
behavioural or pharmacological therapy is below
130/80 mm Hg 2. To reach this goal, most often
combination therapy will be required 3. It is
recommended that all effective and well-tolerated
antihypertensive agents are used, generally in
combination 4. Available evidence indicates that
renoprotection benefits from the regular
inclusion in these combinations of an ACE
inhibitor in type 1 diabetes and of an
angiotensin receptor antagonist in type 2
diabetes
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2003 European Society of Hypertension European
Society of Cardiology guidelines for the
management of arterial hypertension Antihypertensi
ve therapy in diabetics (II)
5. In type 2 diabetic patients with high normal
blood pressure who may sometimes achieve blood
pressure goal by monotherapy, the first drug to
be tested should be a blocker of the renin
angiotensin system 6. The finding of
microalbuminuria in type 1 or 2 diabetics is
an indication for antihypertensive treatment,
especially by a blocker of the renin angiotensin
system, irrespective of the BP values
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DIABETIC HYPERTENSION Combinations of two or
more drugs are usually needed to achieve the
target goal of lt130/80 mmHg. Thiazide diuretics,
BBs, ACEIs, ARBs, and CCBs are beneficial in
reducing CVD and stroke incidence in patients
with diabetes. ACEI- or ARB-based treatments
favorably affect the progression of diabetic
nephropathy and reduce albuminuria, and ARBs have
been shown to reduce progression to
macroalbuminuria.
The seventh Report of the Joint National
Committee on Prevention, Detection, Evaluation of
High Blood Pressure, May 2003
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Blood Pressure Management(every visit)Diagnosis
and Rx Target lt 130/80 mm Hg
Nonpharmacologic Therapies Weight management
Physical activity Sodium restriction Smoking
cessation
Hypertension
Normal BP ?CVD Risk
Hypertension with Nephropathy
ACE Inhibitor Target BP lt 130/80 mm Hg
ACE Inhibitor or ARB Target BP lt 130/80 mm Hg
ACE Inhibitor or ARB Target BP lt 125/75 mm Hg
Consider multidrug therapy (required in up to 60
of patients)
Thiazide Low cost Systolic HTN Elderly patients
?-Blocker Effective post-MI Avoid if
severe hypoglycemia
Ca Channel Blocker Systolic HTN ? Non DHP Use
in combination
Other Agents Consider cost Use in combination
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CATEGORY OF RISK BASED ON LIPOPROTEIN LEVELS IN
ADULTS WITH DIABETES
LDL cholesterol
HDL cholesterol
triglyceride
Risk
High Borderline Low

• gt130
• 100-129
• lt100

• lt35
• 35-45
• gt45

• gt400
• 200-399
• lt200

Data are given in mg/dl For women the HDL
cholesterol values should be increased by 10 mg/dl
Diabetes Care, 2002 25 suppl 1
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TREATMENT DECISION BASED ON LDL CHOLESTEROL LEVEL
IN ADULTS WITH DIABETES
Diabetes Care, 2002 25 suppl 1
Medical nutrition therapy
Drug therapy
Initiation level
LDL goal
Initiation level
LDL goal
With CHD, PVD, or CVD Without CHD, PVD, and CVD

• gt100
• gt100

• lt100
• lt100

• gt100
• gt130

• lt100
• lt100

Data are given in mg/dl For patients with LDL
between 100 and 129 mg/dl, a variety of
treatment strategies are available, including
more aggressive MNT and pharmacological treatment
with a statin in addition, if the HDL is lt40
mg/dl, a fibric acid such as fenofibrate may be
used in these patients.MNT should be
attempted before starting pharmacological therapy
(typically reduces LDL 15-25 mg/dl).
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ORDER OF PRIORITIES FOR TREATMENT OF
DIABETICDYSLIPIDEMIA IN ADULTS
1. LDL cholesterol lowering First choice HMGCoA
reductase inhibitor (statin) Second choice bile
acid binding resin (resin) or fenofibrate 2. HDL
cholesterol raising Behavioural interventions
such as weight loss, increased physical
activity and smoking cessation may be
useful Difficult except with nicotinic acid,
which should be used with caution, or
fibrates 3. Triglyceride lowering Glycaemic
control first priority Fibric acid derivative
(gemfibrozil, fenofibrate) Statins are
moderately effective at high dose in
hypertriglyceridemic subjects who also have
high LDL cholesterol
Diabetes Care, 2002 25 suppl 1
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ORDER OF PRIORITIES FOR TREATMENT OF
DIABETICDYSLIPIDEMIA IN ADULTS (II)
4. Combined hyperlipidemia First choice
improved glycaemic control plus high
dose statin Second choice improved glycaemic
control plus statin plus fibric acid derivative
(gemfibrozil, fenofibrate) Third choice
improved glycaemic control plus resin
plus fibric acid derivative (gemfibrozil,
fenofibrate) improved glycaemic control plus
statin plus nicotinic acid (glycaemic control
must be monitored carefully)
Decision for treatment of high LDL before
elevated triglyceride is based on clinical trial
data indicating safety as well as efficacy of the
available agents. The combinatiohn of statins
with nicotinic acid and especially
with gemfibrozil or fenofibrate may carry an
increased risk of myositis
Diabetes Care, 2002 25 suppl 1
27
TREATMENT OF HYPERTRIGLYCERIDEMIA
In the case of severe hypertriglyceridemia (gt1000
mg/dl 11.3 mmol/L) severe dietary fat
restriction (lt10 of calories) (in addition to
pharmacological therapy) is necessary to
reduce the risk of pancreatitis. Above 400 mg/dl
4.50 mmol/L strong consideration should
be given to pharmacological treatment of
triglyceridemia
Diabetes Care, 2002 25 suppl 1
28
Aspirin Therapy in Diabetes
Recommendations

• Use aspirin therapy as a secondary prevention
  strategy
• in diabetic men and women who have evidenc of
  large vessel
• disease
• 2. consider aspirin therapy as a primary
  prevention strategy
• in high risk men and women with type 1 or type 2
  diabetes

Daibetes Care 2002 25S78-S79
29
Aspirin Therapy in Diabetes (II)
These include diabetic subjects with the
following A family history of coronary heart
disease Cigarette smoking Hypertension
Obesity (gt120 desirable weight BMIgt27,3 in
women, gt27,8 kg/m2 in men) Albuminuria (micro
or macro) Lipids (Cholesterol gt200 mg/dl LDL-C
gt100 mg/dl HDL-C lt45 mg/dl in men lt55 mg/dl in
women Triglyceride gt200 mg/dl) Age gt30 years
Daibetes Care 2002 25S78-S79
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Aspirin Therapy in Diabetes (III)
Use of aspirin has not been studied in diabetic
individuals Under the age of 30 years. 3. Use
enteric-coated aspirin in doses of 80-325
mg/day. 4. People with aspirin allergy, bleeding
tendency, anticoagulant therapy, recent
gastrointestinal bleeding and clinically
active hepatic disease are not candidates for
aspirin therapy. 5. Aspirin therapy should not
be recommended for patients under the age of 21
years because of the increased risk of Reyes
syndrome associated with aspirin use in this
population.
Daibetes Care 2002 25S78-S79
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Type 2 DiabetesManagement Goals - Summary

• Reduce macrovascular complications
• Good glycaemic control
• LDL-Cholesterol lt100 mg/dL (Statins)
• BP lt130/80 mm Hg (ACE inhibitors)
• Weight loss 5 to 10 body weight
• ASA
• No Smoking
• Realistic exercise