THANK YOU

7th Conference for Diabetes in Upper Egypt

على اسم مصر التاريخ

يقدر يقول ما يشاء

أنا مصر عندي أحب و

أجمل األشياء

على اسم مصر التاريخ يقدر يقول ما يشاء

أنا مصر عندي أحب و أجمل األشياء

Watching Elephants Fly

conflict of Interest Declaration

No other conflicts to report

and I dislike pharaohs I like Tahreer Square

7th Conference for Diabetes in Upper Egypt

Does reduction of hyperglycemia reduce the risk of cardiovascular disease?

No Yes

Does reduction of hyperglycemia reduce the risk of cardiovascular disease?

Maybe no Maybe yes, but

9

Why Care

Risk reduction of CVD in diabetics

?

Can we prevent CVD risk in diabetics

Risk reduction of CVD in diabetics Primary prevention of diabetes

.

- Hypertension - Dsylipidemia - Obesity - Microalbuminuria - Smoking - Sedentary lifestyle - Diet

Risk reduction of CVD in diabetics

- Hyperglycemia

Targeting all risk factors:

Rationale For Intensive Glycemic Control To Reduce CV Risk

Does hyperglycemia increase the risk of cardiovascular disease?

Does reduction of hyperglycemia reduce the risk of cardiovascular disease?

What is the Evidence?

What is the

Evidence?

HbA1c and Coronary Risk in the EPIC Study

0

1

2

3

4

5

6

7

8

5 5.5 6 6.5 >7 DM

Men Women

Khaw et al Ann Int Med 2004;141:413-420

RR

Does reduction of hyperglycemia reduce the risk of

cardiovascular disease?

1- DCCT Study

2- EDIC Study

Glycemic Control and Prevention of Complications in type 1 diabetes

Why Doesn’t Glucose Reduction Lower the Risk of

Macrovascular Disease?

winston churchill

122 kg Lazy

Legendary gluttony Smoker

Died age 90

68 kg Marathon runner

Healthy lifestyle promoter

Died MI,age 52(while running)

Father died MI age 42

Jim Fixx

Steno-2

Why Doesn’t Glucose

Reduction Lower the Risk of

Macrovascular Disease?

Would more intensive glucose control (targeting

6-6.5%) or longer follow-up result in decreased CV complications?

Would longer follow-up

result in decreased CV complications?

“All Good Things Come

to Those Who Wait”

EDIC Study

NEJ MED JAN - 2006

DCCT/EDIC: Intensive glucose control associated with reduced long-term CV risk

DCCT/EDIC Study Research Group.N Engl J Med. 2005;353:2643-53.

Any initial CV event*

Time (years)

N = 1441 with type 1 diabetes, mean baseline age 27

42% Risk(9%–63%)

P = 0.02

57% Risk(12%–79%)

P = 0.02

CV death, nonfatal MI,

stroke*

52 events

31 events

25 events

11 events

0

0.12

0.08

0.10

0.06

0.04

0.02

0 5 10 15 20

0

0.12

0.08

0.10

0.06

0.04

0.02

0 5 10 15 20

DCCT ends

DCCT endsA1C 7.4% vs 9.1%

Conventional Intensive

Would more intensive

result in decreased CV

complications?

ACCORD TRIAL.

ADVANCE TRIAL.

VADT

Glycemic control and CHD A tale of three studies

Intensive glycemic arm of ACCORD stopped

February 7, 2008

ACCORD & ADVANCE: Differences

ACCORD ADVANCE

Baseline A1C 8.1 7.2

Months to final A1c 12 36

Treatment

Insulin 66% 33%

TZD 75% 14%

ACCORD & ADVANCE: Differences ACCORD ADVANCE

Weight Gain (kg)

Intensive 3.5 0.0

Standard 0.4 -1.0

Severe Hypoglycemia

Intensive 16.2% 2.7%

Standard 5.1% 1.5%

THANK YOU FOR TRYING TO STAY AWAKE

has confused me as to the

relationship of glucose control

and heart disease

The ACCORD study

• Drug-drug interaction

• Imperfect glucose- lowering drugs

• Weight gain

• Hypoglycemia

Potential causes of increased mortality during intensified therapy

ACCORD: putting the results into perspective

One size fits all

Was Mao correct?

One size fits all

One size fits all

With different sizes

One size doesn’t fit all

There has been recent change from “standerdized” to “personalized” approaches

One size doesn’t fit all

Big change from one size fits all

Subgroup analysis

Paradise and small details

The good physician treats the disease; the great physician treats the patient who has the disease. William Osler

12 July 1849 – 29 December 1919

1. Different subgroups may need different goals

2. Randomized controlled trial subgroup analysis

3. It may be rational to treat specific patients at specific times

Subgroup approach

Blood Pressure, Lipids and Glucose in Type 2 Diabetes

How Low Should We Go

European Heart Journal. Sep 2011

Re-Discovering Personalized Care

Recent clinical trials have suggested that

some patient subgroups might respond differently to aggressive risk

factor management. Our challenge is how to identify these patients and deliver truly personalized diabetes care that maximizes benefit and minimizes harm

Blood Pressure, Lipids and Glucose in Type 2 Diabetes How Low Should We Go? Re-Discovering Personalized Care

European Heart Journal. Sep 2011

Subgroup analysis

HR p- value

Prior known CVD 3,116 <0.01

Age 2,090 <0.01

HDL-Cholestrol 0,699 0.01

HbA1c 1.213 0.02

Hypoglycemic epesodes 4,042 0.01

VADT: CVD martality predictors

- Patients had longest duration since diabetes diagnosis at baseline (>10 years)

- Had highest baseline HbA1c concentrations

- Greater risk of hypoglycemia

. ACCORD & VADT mortality, but:

Can we make sense of recent

outcome trials in type 2 diabetes?

• End point HR(95% Cl)

• MACE 0.91(0.84-0.99)

• MI 0.85(0.76-0.94)

• Stroke 0.96(0.83- 1.10)

• CVD death 1.10(0.84-1.42)

• All-cause mortality 1.04(0.9-1.2)

Overall odds ratios for clinical end points in meta-analysis

Glycemic Control & CVD: meta-analysis

•CVD death 1.10(0.84-1.42) •All-cause mortality 1.04(0.9-1.2)

Diabetologia 2009

MACE=CVD non-fatal MI, non-fatal stroke

Subgroup analysis

Pre-specified subgroups

More intensive

Less intensive

Hazard ratio (95% CD)

p value for test of difference

Sex Male Female

Age <65 years ≥65 years

HbA1c <7.5% 7.5% - 8.5% >8.5%

Duration of diabetes <5 years 5 – 10 years >10 years

History of macrovascular disease Present Absent

8,870/849 5,450/345

7,940/851 4,789/325

8,937/573 5,383/621

7,338/518 5,391/658

5,891/423 4,392/343 3,785/406

4,906/405 4,119/376 3,570/389

4,910/334 2,218/249 2,053/257

3,314/279 2,222/248 2,060/276

3,974/555 10,346/639

3,947/544 8,782/632

1,523/222 12,554/940

1,595/223 10,891/917

0.90 (0.82 – 0.99) 0.94 (0.81 – 1.10)

0.89 (0.79 – 1.01) 0.93 (0.83 – 1.04)

0.83 (0.64 – 1.06) 0.84 (0.73 – 0.98) 0.99 (0.86 – 1.14)

0.84 (0.71 – 0.98) 1.00 (0.84 – 1.20) 0.93 (0.78 – 1.10)

1.00 (0.89 – 1.13) 0.84 (0.75 – 0.94)

History of microvascular disease Present Absent

1.02 (0.85 – 1.23) 0.89 (0.81 – 0.98)

0.19

0.04

0.32

0.22

0.64

0.64

Favours more intensive

0.5 2.0 1.0

Hazard ratio (95% CI)

Favours less intensive

Diabetologia 2009

Effects of more- vs less-intensive glycaemic control on CV events by participant group

Subgroup analysis

History of macrovascular disease Present

Absent

1.00 (0.89 – 1.13) 0.84 (0.75 – 0.94)

3,974/555 10,346/639

3,947/544 8,782/632

Favours more intensive

0.5 2.0 1.0

Hazard ratio (95% CI)

Favours less intensive

Diabetologia 2009

Duration of diabetes <5 years 5 – 10 years >10 years

4,910/334 2,218/249 2,053/257

3,314/279 2,222/248 2,060/276

0.84 (0.71 – 0.98) 1.00 (0.84 – 1.20) 0.93 (0.78 – 1.10)

Effects of more- vs less-intensive glycaemic control on CV events

Subgroup analysis

Diagnosis

[UKPDS]

Early treatment should emphasise glucose control and prevention of vascular

disease

Age, vascular complications

[ACCORD, ADVANCE, VADT]

Diagnosis

Later treatment should emphasise non-glycaemic risk factors

Clinically apparent vascular disease

No vascular disease

Disabling vascular disease

PRIMARY prevention

SECONDARY prevention

GLUCOSE

BP, Lipids

What did we learn from the recent megatrials?

● timing: short disease duration

● baseline HbA1c value: 7.5- 8.0%

● age of patient: young/middle aged

● speed and degree of glycemic control: gradual lowering

of HbA1c, and a target HbA1c between 6.5– 7.0%

● co-morbidity: absence of overt CVD of multiple CVD risk factors.

● patient-specific conditions: education, finance and family support.

Criteria in favour of intensive glycemic control

MY Take Home

Message:

Was Mao correct?

MY Take Home Message:

THANK YOU

شكرا

THANK YOU