1) The document discusses several studies and trials related to the relationship between glucose control and cardiovascular disease risk in diabetics. 2) Subgroup analyses from some trials suggested that more intensive glucose control may benefit some patient subgroups but not others, depending on factors like age, disease duration, and presence of vascular complications. 3) Recent evidence emphasizes the need for personalized treatment targets and management based on individual patient characteristics and risk factors rather than a "one size fits all" approach to glucose control.

2. THANK
YOU
7th Conference for Diabetes in Upper Egypt

3. ‫التاريخ‬ ‫مصر‬ ‫اسم‬ ‫على‬
‫يشاء‬ ‫ما‬ ‫يقول‬ ‫يقدر‬
‫و‬ ‫أحب‬ ‫عندي‬ ‫مصر‬ ‫أنا‬
‫األشياء‬ ‫أجمل‬

4. Watching Elephants Fly

6. conflict of Interest Declaration
No other conflicts to report
and I dislike pharaohsI like Tahreer Square
7th Conference for Diabetes in Upper Egypt

7. Does reduction of hyperglycemia reduce
the risk of cardiovascular disease?
No
Yes

8. Does reduction of hyperglycemia reduce
the risk of cardiovascular disease?
Maybe no
Maybe yes,
but

9. 9
Why Care
Risk reduction
of CVD in
diabetics
?

11. Can we prevent CVD risk in diabetics

12. Risk reduction of CVD in diabetics
Primary prevention of diabetes

13. .
- Hypertension
- Dsylipidemia
- Obesity
- Microalbuminuria
- Smoking
- Sedentary lifestyle
- Diet
Risk reduction of CVD in diabetics
- Hyperglycemia
Targeting all risk factors:

14. 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?

15. What is the
Evidence?

16. 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

17. Does reduction
of hyperglycemia
reduce the risk of
cardiovascular
disease?

18. 1- DCCT Study
2- EDIC Study
Glycemic Control and Prevention of
Complications in type 1 diabetes

20. Why Doesn’t
Glucose Reduction
Lower the Risk of
Macrovascular
Disease?

21. 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

23. Steno-2

25. Why Doesn’t
Glucose
Reduction Lower
the Risk of
Macrovascular
Disease?

26. Would more
intensive glucose
control (targeting
6-6.5%) or longer
follow-up result
in decreased CV
complications?

27. Would longer
follow-up
result in decreased
CV complications?

28. “All Good
Things Come
to Those
Who Wait”

29. EDIC Study
NEJ MED
JAN - 2006

30. 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

32. Would more
intensive
result in
decreased CV
complications?

33.  ACCORD TRIAL.
 ADVANCE TRIAL.
 VADT
Glycemic control and CHD
A tale of three studies

36. Intensive glycemic arm of ACCORD
stopped
February 7, 2008

39. ACCORD & ADVANCE: Differences
ACCORD ADVANCE
Baseline A1C 8.1 7.2
Months to final A1c 12 36
Treatment
Insulin 66% 33%
TZD 75% 14%

40. 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%

41. THANK YOU FOR TRYING TO STAY
AWAKE

46. has confused me
as to the
relationship of
glucose control
and heart
disease
The ACCORD study

47. • Drug-drug interaction
• Imperfect glucose-
lowering drugs
• Weight gain
• Hypoglycemia
Potential causes of increased mortality
during intensified therapy

50. ACCORD:
putting the
results into
perspective

51. One size fits all

52. Was Mao correct?

53. One size fits all

54. One size fits all

56. With different sizes

57. One size doesn’t fit all

58. There has been recent change from
“standerdized” to “personalized”
approaches
One size doesn’t fit all
Big change from one size fits all

60. Subgroup analysis

61. Paradise and small details

62. The good
physician treats
the disease; the
great physician
treats the patient
who has the
disease.
William Osler
12 July 1849 – 29 December 1919

63. 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

64. Blood Pressure, Lipids and
Glucose in Type 2 Diabetes
How Low Should We Go
European Heart Journal. Sep 2011
Re-Discovering Personalized Care

65. 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

66. Subgroup analysis

69. 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

70. - Patients had longest duration since diabetes
diagnosis at baseline (>10 years)
- Had highest baseline HbA1c concentrations
- Greater risk of hypoglycemia
. ACCORD & VADT mortality, but:

71. Can we make
sense of recent
outcome trials in
type 2 diabetes?

72. • 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

73. Subgroup analysis

74. 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 2.01.0
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

75. 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 2.01.0
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

76. Diagnosis
[UKPDS]
Early treatment should emphasise glucose
control and prevention of vascular
disease

77. Age, vascular complications
[ACCORD, ADVANCE, VADT]
Diagnosis
Later treatment should emphasise
non-glycaemic risk factors

78. Clinically apparent
vascular disease
No vascular disease
Disabling
vascular disease
PRIMARY
prevention
SECONDARY
prevention
GLUCOSE
BP, Lipids

80. What did we learn from
the recent megatrials?

88. ● 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

90. MY Take
Home
Message:

91. Was Mao correct?

92. MY Take Home Message:

93. THANK
YOU
‫شكرا‬

94. THANK YOU