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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
conflict of Interest Declaration
No other conflicts to report
and I dislike pharaohs I like Tahreer Square
7th Conference for Diabetes in Upper Egypt
.
- 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?
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
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
Would more intensive glucose control (targeting
6-6.5%) or longer follow-up result in decreased CV complications?
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
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%
• Drug-drug interaction
• Imperfect glucose- lowering drugs
• Weight gain
• Hypoglycemia
Potential causes of increased mortality during intensified therapy
There has been recent change from “standerdized” to “personalized” approaches
One size doesn’t fit all
Big change from one size fits all
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
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:
• 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
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
● 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