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ARS QUESTION
Case 1: Poorly Controlled Type 2
Diabetes on No Treatment
ARS QUESTION
Case 1: Poorly Controlled Type 2
Diabetes on No Treatment
ARS QUESTION
Case 2: Poorly Controlled Type 2 Diabetes
on OHA 4. Bolus insulin with the largest
meal (~6 U)
Case 2: Poorly Controlled Type 2 Diabetes
on OHA 4. Bolus insulin with the am and pm
meals
Basal/Bolus Treatment Program with
Rapid-acting and Long-acting Analogs
Or Or Or
Glulisine Glulisine Glulisine
Glargine
or
Detemir
Adapted from Bode B. Medical Management of Type 1 Diabetes. 4th ed. Alexandria, Va: American Diabetes Association; 2004.
Inhaled Insulin vs Rosiglitazone in
DM–2 Patients on Diet Alone
N=76 N=69
P<0.01
10
A1C, %
10 P=0.03 N=16
Baseline
9
6 months
A1C, %
5
Insulin Aspart Premeal NPH or 70/30 BID
0.42 U/kg 0.67 U/kg
3-kg Weight Gain 1-kg Weight Gain
ARS QUESTION
Case 3: Poorly Controlled Type 2
Diabetes on OHA
0 Time (wk) 24
Baseline End Point
*Sulfonylurea + metformin
OAD=oral antidiabetic drug
Janka HU, et al. Diabetes Care. 2005;28:254-259.
Insulin Glargine Plus OADs vs
Twice-daily Premixed Human Insulin
Change in A1C from Baseline to Study End Point*
P=0.0003 Baseline
9 24 week
8.85 8.83
8
A1C 7.49
7 7.15
5
Insulin glargine + OAD Premixed
*Intent-to-treat analysis
OAD=oral antidiabetic drug
10
9.9
8
# of Episodes
6
Per
Patient-Year 4 4.1
2
0
Insulin Glargine + OAD Premixed
n = 233
Type 2 DM
Glargine OD (10 U, bedtime) + metformin +/- TZD
BMI ≤ 40 kg/m2
Body weight ≤125 kg
HbA1C ≥ 8.0% Titrate to 80 to 110 mg/dL
on metformin +/- TZD
4 wk run-in:
Stop insulin secretagogues and α -glucosidase inhibitors
Optimize metformin to ≥1500 mg/day
Switch rosiglitazone for 30 mg pioglitazone
-4 0 28
(Weeks)
Raskin P, et al. Diabetes Care. 2005;28:260-65
Glargine vs Twice-daily Analog mix 70/30
Insulin with Metformin ± Pioglitazone
Change in A1C From Baseline to Study End Point*
9.8 9.7 Baseline
P <0.01
9 9.8 9.7 28 week
8
A1C
7.4
7
6.9
5
Insulin Glargine + OAD Premixed + OAD
300
250 Baseline
200
* *
150
+ * *
Week 28
100
50
BB B90 BL L90 BD D90 Bed 3am
∗ BIAsp 70/30 lower BG vs glargine p<0.05
+ Glargine lower BG vs BIAsp 70/30, p<0.05
Raskin P, et al. Diabetes Care. 2005;28:260-265.
INITIATE – Rate of Overall Hypoglycemia
(events per patient-year)
Minor hypoglycemia
N (subjects) 50 19
Mean rate 3.4 ± 6.6 0.7 ± 2.0 <0.05
Final insulin dose: 78.5 U (0.82 U/kg) for BIAsp 30 and 51.3 U (0.55 U/kg) for Glargine
Weight Gain (kg): 5.4 ± 4.8 for BIAsp 30 and 3.5 ± 4.5 for Glargine
ARS QUESTION
Case 4: Poorly Controlled Type 2
Diabetes on Glargine Insulin at HS
ARS QUESTION
Case 5: Poorly Controlled Type 2
Diabetes on MDI
Less pain
Flexibility
Convenience
Less burden
-5 0 5 10 15 20 25 30 35
Change in scores (raw units) from baseline to endpoint
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))) ) )
))) Paradigm 715™
Paradigm Link™
Wizard: On
Carb units: Carb
Carb ratio: 1
BG units: mg/dL
Sensitivity: 15
BG target: 80–100
Active insulin time: 5h
Case 6: New-onset Diabetes
ARS QUESTION
Case 6: New-onset Diabetes
ARS QUESTION
LADA: Detection and
Impact of GAD Antibodies
Genetic
Antibody
predisposition
Progressive loss
of insulin release
Normal insulin
release Overt diabetes
Glucose
Beta- normal
C-peptide
cell
present
mass
No C-peptide
present
Age (y)
Adapted from: Atkinson. Lancet. 2002;358:221-229.
Case 6: New-onset Diabetes
• Sees me the following morning
(BG 514, urine ketones small)
• I concur with him that he has type 1 diabetes
and metformin is not the treatment, insulin is
• What is your initial treatment?
1. IV insulin
2. Premixed
3. Basal/bolus therapy by MDI
4. Insulin pump therapy
ARS QUESTION
Options in Insulin Therapy
for Type 1 Diabetes
• Current
— Multiple injections
— Insulin pump (CSII)
DCCT Absolute Risk of Retinopathy:
Conventional vs Intensive Insulin Therapy
• At the same A1C level, intensive insulin therapy provides
a greater risk reduction of the development of retinopathy
Development of Retinopathy
Conventional Therapy Intensive Therapy
24 24
11% 10%
Rate Per 100 Patient-Years
Mean A1C
20 9% 20
16 16
12 12
8% Mean A1C
8 8 9%
7%
4 4 8%
7%
6%
0 0
0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9
Time During Study (y)
DCCT Research Group. Diabetes. 1995;44:968-983.
Intensive Insulin Therapy Preserves
Beta Cell Function
1.0
0.9
0.8
Patient Probability
C-peptide >2.0
of Maintaining
0.7
0.6
0.5
0.4
0.3 Intensive therapy
0.2
0.1 Conventional
therapy
0.0
0 1 2 3 4 5 6
Years Postenrollment
Number of evaluated patients in each treatment group
Intensive 108 131 80 53 32 8 2
Conventional 165 150 63 32 22 3 0
14.0
13.0
12.0
A1C
Case 6: New-onset Diabetes on CSII