Insulin Therapy For Type 2 Diabetes Mellitus: Akhmad Nurdani
Insulin Therapy For Type 2 Diabetes Mellitus: Akhmad Nurdani
Insulin Therapy For Type 2 Diabetes Mellitus: Akhmad Nurdani
Akhmad Nurdani
• insulin secretion
• insulin resistance
80
Islet -cell function
60
Pancreatic function
40
= 50% of normal
20
0
10 9 8 7 6 5 4 3 2 1 0 1 2 3 4 5 6
Years
HOMA = homeostasis model assessment
80
60
40
0
0 1 2 3 4 5 6 0 1 2 3 4 5 6
Years from randomization
Inadequate therapy
Change
Paradigm
“Treat to Succeed”
“Treat to fail”
Physiologic Glucose Homeostasis and Insulin
0 Basal insulin
9.0
Glucose
6.0
Glucose
(mmo/L) 3.0
Basal glucose
0
7 8 9 10 11 12 1 2 3 4 5 6 7 8 9
a.m. p.m.
Time of Day
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Glucose is the primary stimulator of insulin secretion
IR signaling pathways.
(Humulin R, Actrapid)
(Humulin N, Insulatard)
(Lantus,
Levemir)
Unwanted
hypoglycemia periode
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Treat-to-Target: addition of detemir or
NPH to oral therapy
475 People with Type 2 Diabetes on 1 or 2 Oral Agents
-0.5
HbA1c
8
-1.0
NPH
-1.5 4
detemir
-2.0 -1.8%
-1.9%
P=NS 0
Final HbA1c 6.6% 6.8% 5.0 6.0 7.0 8.0 9.0
Insulin detemir
Hermansen K et al. Diabetes Care. 2006;29:1269-1274
Addition of glargine or biphasic
aspart to oral therapy
233 People with Type 2 Diabetes on 1 or 2 Oral Agents
Glycaemic Control Hypoglycaemia
Baseline HbA1c 9.7% 9.8% 4 P<0.05
0.0 3.4
Events/Patient-year
-0.5
-1.0
-1.5 2
-2.0
1 0.7
-2.5 -2.4%
-3.0 -2.8%
0
P<0.01
Final HbA1c 6.9% 7.4%
Mean (±SE) Percentage Change from Baseline to 1 Year in Glycated Hemoglobin, Fasting Plasma
Glucose, Postprandial Glucose, and Body Weight (Panel A) and Mean (+SD) Hypoglycemic-Event
Rate (Panel B)
4-T Study Group, N Engl J Med 2007;357:1716-30
Basal-bolus insulin treatment: matching
insulin administration to insulin needs
Rapid-acting insulins
100
B L D Basal insulins
80
μU/ml
60
40
Normal pattern
20
Time of day
5
Patients (%)
4 3.8%
2
1.2%
1
0.1% 0.3%
0
Diet Sulfonylurea Metformin Basal Basal +
insulin prandial
insulin
Decreased
Incretin Effect
Increased
Impaired Lipolysis
Insulin Secretion
Islet a-cell
Increased
Decreased Glucose
HGP
Neurotransmitter Uptake
DeFronzo Diabetes 2008
Dysfunction
Summary of available
insulin preparations
Glucose lowering
Suboptimal insulin
therapy
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Normal Blood Glucose Levels
8-
6-
4-
2-
Time
www.diabetesclinic.ca
Normal Blood Glucose Levels
8-
6-
4-
2-
Time
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Blood Glucose (mmols)
10-
Two injections/day
8-
6-
4-
2-
R or H + N in AM R or H + N at Supper
0
Time
www.diabetesclinic.ca
Blood Glucose (mmols)
10-
Three injections/day
8-
6-
4-
2- R or H + N in R or H at N before bed
AM Supper
0
Time
www.diabetescl 46
Blood Glucose (mmols)
6-
4-
2-
R or H at every meal N or U once or twice/day
0
www.diabetescl 47
Continuous Infusion
Blood Glucose (mmols)
10-
8-
6-
4-
2-
Time
www.diabetesclinic.ca
What should I tell the person with Type
2 diabetes who needs
insulin, but doesn’t want to take it?
N
Western regimen
S
Two doses: 150
6 9 12 3 6 9 12 3
I
Three doses: 150
I
6 9 12 3 6 9 12 3
N Four doses: 150
6 9 12 3 6 9 12 3
C
Four doses: 150
6 9 12 3 6 9 12 3
O
N
N
Western regimen
S
Two doses: 150
6 9 12 3 6 9 12 3
I
Three doses: 150
I
6 9 12 3 6 9 12 3
N Four doses: 150
6 9 12 3 6 9 12 3
C
Four doses: 150
6 9 12 3 6 9 12 3
O
N
formulation hexamers dimers monomers
capillary membrane
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Limitations of Regular Human Insulin
www.diabetesclinic.ca
Advantages of Rapid-Insulin Analogues
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Insulin Glargine
Long Acting-Insulin Analogue
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OAD Interventions as monotherapy
During progression of disease, loss of glucose control with oral agents results in glucose toxicity
and worsening pathophysiology. In experimental models, prolonged exposure to hyperglycemia
has been shown to result in glucotoxicity and oxidative stress, culminating in β-cell destruction
and microvascular and macrovascular complications
The timely addition of insulin to oral agents can prevent this cycle of disease progression and
eliminate the “stuttering” pattern of loss of glycemic control.
What should I tell the person with Type
2 diabetes who needs
insulin, but will not take injections?
‘Most people who do not want to take injections are
happy using them after giving their first injection; but non-
injectable forms of insulin are also available now, and I
can show you both so you can choose.’
-0.2%
-0.5
HbA1c (%)
-1.0
* INH
OA
-2.0 -1.9%
*
INH = inhaled insulin; OA = secretagogue + metformin or TZD
*P<0.0001 vs OA
Rosenstock J et al. Ann Intern Med. 2005;143:549-558
Mealtime inhaled insulin or
metformin added to sulfonylurea
427 People on Sulfonylurea with HbA1c 8.0% to 12.0%
Baseline HbA1c 8.8% 8.8% 10.5% 10.6%
0.0
-0.5
HbA1c (%)
-1.0
-1.5
-2.0 -1.8%
-1.9% -1.9%
INH + SU -2.2%
-2.5 P=0.002
Met + SU
Overall
Satisfaction Ease of Use Social Comfort
P<0.01
Treatment satisfaction (%)
50 P<0.01 NS
43.2%
37.9% 39.3%
40
30
20
8.7%
10
3.1%
0
-0.9%
-10 Inhaled insulin (n=60)
SC human insulin (n=61)
1 mg 3U 1 —
2 mg 6U 2 —
3 mg 8U — 1
4 mg 11 U 1 1
5 mg 14 U 2 1
6 mg 16 U — 2
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The widespread decrease in glycemic control
Percentage of adults with diabetes who have achieved target glycemic, blood pressure,
and total cholesterol levels as reported in the National Health and Nutrition Examination
Surveys (NHANES III and NHANES 1999-2000).
J Am Osteopath Assoc. 2007;107:260-269
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Stepwise Intensification of Treatment
for Continuity of Control