Professional Documents
Culture Documents
2004 (4)
Qualtity of Life
Quality of Life
Perspective in Life
By patients
1
Expectation of Life
Dreyer,1997
Reliev symptoms
Maintain normal weight
Achieve normal activity
Maintain normal blood glucose levels (70
140 mg%)
Achieve acceptable HbAIc (< 7%)
Prevent long-term and short-term
complications
Prevent hypoglycemic and hyperglycemic
reactions
Normal
Goal
Additional Action
Suggested
(mg/dl)
Plasma value
Average preprandial
Average bedtime
< 100
< 120
90 130
110 150
Whole blood
Average preprandrial
Average bedtime
< 100
< 110
80 120
100 140
80 or > 140
< 100 or > 160
AIC
< 6%
<7
>8
Blood pressure
Lipids
- LDL
- Triglycerides
- HDL
mmol/L
133
170
205
240
275
310
345
7.5
9.9
11.5
13.5
15.5
17.5
19.5
Treatment of DM
Nutrition Therapy, Exercise, Lifestyle
Changes
Pharmacological Treatment
- Insulin
- Oral diabetes medications
Pancreas/Islet-cell transplantations
Education
Exercise
increase energy expenditure with
moderate-intensity exercise
PHARMACOTHERAPY
Oral Diabetic Medications
-cell dysfunction
Insulin resistance
Insulin
Secretagogues
Insulin
Sensitizer
Insulin basal
Sulfonylureas
Metformin
Insulin prandial
Glinide
Glitazones
(-Glucosidase
inhibitors)
Metformin
Liver
Receptor +
postreceptor defect
Glucose
Muscle
Insulin
resistance
Glucose uptake
Prandial plasma
glucose
Insulin
resistance
Glucose production
Fasting plasma glucose
Pancreas
Fat
Glitazones
Insulin Secretagogues
MECHANISM OF ACTION
Sulfonylureas: Efficacy
Approximately 50% of patients with newly
diagnosed type 2 diabetes achieve
acceptable glycemic control
About 15%-20% of patients have little or no
glycemic response
1997 PPS
Nateglinide Controlled
Postprandial Spikes
Nateglinide Controlled
Postprandial Spikes
INSULIN SENSITIZER
- Predominant Action in the Liver (Metformin)
- Predominant Action in the Peripheral InsulinSensitive Tissues (Thiazolidine diones)
METFORMIN
Metformin Monotherapy:
Effects on Lipids
10
5
Mean
change
from
baseline (%)
0
-1
-2
-5
Metformin (n=143)
-10
-15
-11*
-11*
Placebo (n=146)
-17
-20
Total-C
LDL-C
Triglycerides
HDL-C
*P<0.05 vs placebo
1998 PPS
20
40
20
Glyburide
Metformin
-20
-20
Diet + metformin
-40
-60
0
13 17
21 25 29
Week
-40
Metformin + glyburide
-60
-80
13 17
21 25 29
Week
*P<0.001
1998 PPS
FPG
100
50
Change
0
after
treatment
(mg/dL) -50
Change
0
after
treatment
-1
-100
-2
Placebo Metformin
-3
Placebo
Metformin
P<0.001; mean SD
Thiazolidinediones
(Glitazones)
FBG (mg/dl)
from baseline)
(mg/dl)
( from baseline)
40 60
30.3
53
24 48
25 55
20 55
20 30
Potentially
normalized
.
56.5
.
.
.
.
20 74
Potentially
normalized
1 2%
1.1%
1 - 2%
0.2 1%
0.1 0.7%
0.3 0.9%
0.5 0.1
Potentially
normalized
FPG
HbA1c
180
Median
160
FPG
(mg/dL)
140
Median
HbA1c
(%)
120
6
0
100
Time from randomization (y)
6
0
0
6
9
12
15
Time from randomization (y)
10-year cohort
Cross-sectional
Patients followed for 10 years
All patients assigned to regimen
Conventional
Conventional
Intensive
Intensive
UKPDS Group. Lancet. 1998;352:837-853.
Primary failure
rate
Secondary
failure rate
15 30%
5 10%/year
< 10%
5 10%/year
Dependent on diet
adherence
Unknown
As high as 25%
Unknown
Feingloss,1999
COMBO
(SU + Metformin)
Titrate dose
te
a
r
le
months
ce
T
c
N
A
CE
E
R
T
Add 3rd OHA
S
PA(Combo)
Begin Insulin
(Continue 1 OHA)
Titrate dose
Begin Insulin
(Continue 1 OHA)
Titrate dose
RULE OF COMBINATION
2 Drugs (or more ?) With
Different Mechanisms of Action
SULFONYLUREA + METFORMIN
METFORMIN + THIAZOLIDINEDIONE
INSULIN + ANY OTHER DRUGS
Insulin resistance
Insulin
Secretagogues
Insulin
Sensitizer
Glibenclamide
Metformin
T
Add 3rd OHA
S
PA(Combo)
Begin Insulin
(Continue 1 OHA)
Titrate dose
COMBO
(SU + Metformin)
Titrate dose
months
te
a
r
le
Begin Insulin
ce
c
T
A
N
CE
E
R
Begin Insulin
(Continue 1 OHA)
Titrate dose
1 OHA
Titrate dose
N
A
TH
O
Y
K
O
F
U
U
O
Y
R
E
T
T
RA
N
O
I
NT
Low risk
Arterial risk
Microvascular
risk
6.5
>6
> 7.5
110
> 110
126
5.5
7.5
> 5.5
> 7.5
> 110
9.0
At risk
4.8 6.0
3.0 4.0
1.0 1.2
1.7 2.2
High risk
6.0
4.0
< 1.0
> 2.2
< 25
< 24
Low risk
< 4.8
< 3.0
< 1.2
< 1.7
< 140/85
(European Diabetes Policy Group. Diabetes Med 1999; 16: 716-30)
Normal
Goal
Additional
action needed
>7
>8
100
< 110
126
100
140
< 110
90 - 130
> 110
9.0
Border line
4.8 6.0
3.0 4.0
1.0 1.2
1.7 2.2
High risk
6.0
4.0
< 1.0
> 2.2
< 23
< 22
Low risk
< 4.8
< 3.0
< 1.2
< 1.7
< 130/80
su
lin
Ac
ti o
Type 2
Diabetes
Insulin
Concentration
-cell
Dysfunction
ia
em
a
yc
l
rg
e
p
y
-cell Failure H
Insulin
Resistance
Euglycaemia
Normal
IGT Obesity
Diagnosis of
type 2 diabetes
Progression of
type 2 diabetes
25%
50%
Metformin
soluble matrix
75%
Glibenclamide
particle range