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Insulin Therapy Case Studies

Bruce W. Bode, MD, FACE


Atlanta Diabetes Associates
Atlanta, Georgia
Case Studies in Diabetes

• All of these cases are real patients


• Names have been deleted to protect patient
identity
• In your answers, assume all are new patients to
your practice
Case 1: Poorly Controlled Type 2
Diabetes on No Treatment

• 40-year-old African-American male diagnosed


with diabetes 6 months ago on admit for MI
• Current treatment: None for diabetes
• Current exam:
— Wt 201 lbs, Ht 69”, BMI 29
— A1C 13%, BG 497, Cr 1.3, ketones negative
• Current complications:
— Hyperlipidemia, CAD
Case 1: Poorly Controlled Type 2
Diabetes on No Treatment

• What is your goal for glucose?


1. 90 to 130 mg/dL premeal,
<180 mg/dL postmeal
2. 80 to 110 mg/dL premeal,
<140 mg/dL postmeal
3. 70 to 100 mg/dL premeal,
<120 mg/dL postmeal

ARS QUESTION
Case 1: Poorly Controlled Type 2
Diabetes on No Treatment

• What is your treatment in addition to diet and


exercise?
1. One oral agent
2. Two oral agents
3. Basal insulin
4. Premixed insulin
5. Basal bolus therapy

ARS QUESTION
Case 1: Poorly Controlled Type 2
Diabetes on No Treatment

• Patient refused insulin


• Placed on glimepiride and metformin
• A1C 6.8% in 3 months; patient quit sweet tea,
colas, and orange juice
• Lesson learned:
— Do not underestimate the power of diet and
exercise
Case 2: Poorly Controlled Type 2
Diabetes on OHA

• 46-year-old Indian man with diabetes since age


33, on max doses of rosiglitazone, glyburide
and metformin; diet balanced; daily exercise
• Current exam:
— Wt 167 lbs, Ht 69.5”, BMI 24
— A1C 8.0%, Cr 1.1, C-peptide 2.6 ng/mL
• Current complications:
— Vitrectomy OD, proteinuria, hyperlipidemia
Case 2: Poorly Controlled Type 2
Diabetes on OHA

• A1C 8.0%; SMBG 1/d; avg 110 mg/dL fasting;


random BG 300 after breakfast
• What treatment do you recommend?
1. Basal insulin morning (~10 U)
2. Premixed insulin morning (~10 U)
3. Premixed insulin morning and evening (~5 U BID)
4. Bolus insulin with the largest meal (~5 U)
5. Starch blocker or glinide (repaglinide or nateglinide)

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

Breakfast Lunch Dinner


Aspart, Aspart, Aspart,
Lispro Lispro Lispro
Plasma Insulin

Or Or Or
Glulisine Glulisine Glulisine

Glargine
or
Detemir

4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00


Time

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, %

9 1.8-kg Weight Gain 0.8-kg Weight Gain

Defronzo R, et al. Accepted for publication. Diabetes Care. 2005.


Insulin Aspart Premeal with Metformin
and Rosiglitazone vs Conventional Insulin

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

Poulsen MK, et al. Diabetes Care. 2003;26:3273-3279.


Starting With Basal Insulin in DM 2 –
Advantages

• Use when fasting BG >140 mg/dL


• 1 injection with no mixing
• Insulin pens for increased acceptance
• Slow, safe, simple titration
• Low dosage
• Effective improvement in glycemic control
• Limited weight gain
Case 3: Poorly Controlled Type 2
Diabetes on OHA

• 80-year-old white man with diabetes since


age 60, on repaglinide 4 mg TID; hx of CHF
• Supportive daughter and wife
• Current exam:
— Wt 175 lbs, ht 72”, BMI 23.5
— A1C 9.2%, Cr 2.7, C-peptide 5.3 ng/mL
• Current SMBG 2.7 tests/d avg 246 mg/dL:
• 178 morning, 206 noon, 247 evening, 271 HS
Case 3: Poorly Controlled Type 2
Diabetes on OHA

• What is your recommendation?


1. Basal insulin
2. Bolus insulin
3. Premixed insulin
4. Basal bolus therapy

ARS QUESTION
Case 3: Poorly Controlled Type 2
Diabetes on OHA

• I chose analog mix 70/30:


— Patient did well titrated to 24 units morning,
14 units evening with SMBG 4/d
— Saw RD, weight increased 5 pounds in 1 month
with A1C 7.2% at 3 months
Case 3: Poorly Controlled Type 2 Diabetes
on OHA 4. Analog Premixed Insulin
Insulin Glargine Plus OADs vs
Twice-daily Premixed 70/30 Human Insulin
Treatment Regimen
Target: FPG ≤ 100 mg/dL
Subjects (n=364) were randomly assigned to:

Insulin glargine once daily + continued OADs


OADs*
Premixed human insulin 70/30 BID

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

Janka HU, et al. Diabetes Care. 2005;28:254-259.


Less Hypoglycemia With Glargine Plus
OADs vs Twice-daily Premixed 70/30 Human
Insulin
Documented Hypoglycemic Episodes Per Patient-Year
P<0.0001

10
9.9
8

# of Episodes
6
Per
Patient-Year 4 4.1
2

0
Insulin Glargine + OAD Premixed

Average dose = 28.2 IU with G + OAD vs 64.5 IU with premixed insulin


Weight Gain: 1.4 ± 3.4 kg with G + OAD vs 2.1 ± 4.2 kg with pre mixed insulin

Janka HU, et al. Diabetes Care. 2005;28:254-259.


The INITIATE study:
Analog Mix 70/30 (BID) vs glargine (QD)

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

NovoMix® 30, pre-breakfast (5 or 6U) and pre-dinner


(5 or 6U) + 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

Raskin P, et al. Diabetes Care. 2005;28:260-265.


INITIATE
8-Pt BG Profiles - Baseline and Wk 28
350 BIAsp 30 Glargine
Blood Glucose (mg/dl)

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)

BIAsp 30 Glargine P value


All hypoglycemia
N (subjects) 82 57
Mean rate 9.8 ± 17.1 4.7 ± 11.4 <0.05

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

Raskin P, et al. Diabetes Care. 2005;28:260-265.


Case 4: Poorly Controlled Type 2
Diabetes on Glargine Insulin at HS

• 49-year old-white woman with diabetes since


age 37, on glargine insulin at HS for 3 years
• Current exam:
— Wt 223 lbs, Ht 65”, BMI 37
— A1C 11.6%, Cr 1.2, C-peptide 2.9 ng/mL
• Current treatment:
— Repaglinide 4 mg AC, glargine 47 U HS
— Cannot tolerate metformin or TZD
Case 4: Poorly Controlled Type 2
Diabetes on Glargine Insulin at HS

• Diet history: Not great; a lot of high-fat, high-


carb food with sweets
• Glucose logs: SMBG 1/d; avg >300 mg/dL
• Activity history: Minimal, married, husband a
drug rep
Case 4: Poorly Controlled Type 2
Diabetes on Glargine Insulin at HS

• In addition to diabetes training and


management by CDEs, what is the next
treatment?
1. Change to analog mix BID
2. Add bolus insulin to largest meal
3. Add bolus insulin to each meal
4. Insulin pump therapy

ARS QUESTION
Case 4: Poorly Controlled Type 2
Diabetes on Glargine Insulin at HS

• Sent for intensive management training in MDI


and diet
• Results 3 months later:
— SMBG 6.5/d = 121 mg/dL
— A1C 6.5%
— On aspart AC: 10 U morning, 7 U noon, 7 U
evening; glargine 40 U HS
Case 4: Poorly Controlled Type 2 on Lantus
Case 5: Poorly Controlled Type 2
Diabetes on MDI

• 55-year-old African-American woman with


diabetes since age 19; on insulin for 15 years
• Current exam:
— Wt 202 lbs, ht 68”, BMI 30
— A1C 15.9%, Cr 0.9, C-peptide 5.5 ng/mL
• Current treatment:
— Lispro AC: 25 U morning, 15 U noon, 15 U evening;
glargine HS: 85 U
— Metformin 1000 mg BID
Case 5: Poorly Controlled Type 2 DM on MDI
Case 5: Poorly Controlled Type 2
Diabetes on MDI

• Diet history: Not great; a lot of high-fat food;


3 colas per day since age 10
• Glucose logs: SMBG 4/d; average >300 mg/dL
• Activity history: Sits for elderly disabled people;
no formal exercise; supportive, caring son in
health care
Case 5: Poorly Controlled Type 2
Diabetes on MDI

• What treatment now?


1. Gastric bypass
2. Atkins diet
3. Find another doctor
4. Trial with insulin pump therapy

ARS QUESTION
Case 5: Poorly Controlled Type 2
Diabetes on MDI

• Elected for CSII


• Started at 75% TDD or 110 U/d
— Basal: 2.0 U/h
— Bolus: 25 U, 15 U, 15 U
— Correction bolus: BG –100/15
Case 5: Poorly Controlled Type 2 DM on MDI
Case 5: Poorly Controlled Type 2
Diabetes on MDI

• Follow-up 3 months postpump start:


— A1C 9%
— SMBG 3.1/d
CSII vs MDI in DM 2 Patients
CSII MDI

Less pain

Fewer social limitations


Preference
Advocacy
Less hassle
Less life interference
General satisfaction

Flexibility
Convenience

Less burden

-5 0 5 10 15 20 25 30 35
Change in scores (raw units) from baseline to endpoint

Testa et al. Diabetes. 2001;50(suppl 2):1781


Smart Pumps Bolus Calculator:
Meter-entered

) ) )) )
))) ) )
))) Paradigm 715™

Paradigm Link™

• Monitor sends BG value to pump via radio


waves – No transcribing error
• Enter carbohydrate intake into pump
• “Bolus Wizard” calculates suggested dose
Paradigm Link® and Paradigm 715® are registered trademarks of Medtronic MiniMed.
Bolus Wizard Set-up Screen

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

• 45-year-old male lawyer presents with “polys”


and weight loss
• Sees internist who recommends metformin
(blood glucose 500, urine ketones small,
BMI 26)
• Patient does some Internet reading and seeks
a second opinion from diabetes specialist who
was a high school classmate he has not seen
for 27 years
Case 6: New-onset Diabetes

• What type of diabetes does he have?


1. Type 1
2. Type 1.5
3. LADA
4. Type 2
5. 1, 2, or 3

ARS QUESTION
Case 6: New-onset Diabetes

• What other diagnostic tests do you need?


1. Islet-cell antibody panel (ICA, anti-GAD)
2. Serum C-peptide
3. Insulin level
4. HLA typing

ARS QUESTION
LADA: Detection and
Impact of GAD Antibodies

• GAD: glutamic acid decarboxylase


• Other antibodies
— ICA, IA2, insulin autoantibodies
• 7% of patients screened in the Treat to Target
Study had GAD antibodies
• 95% of patients in the UKPDS who were anti-
GAD or anti-IC required insulin within 6 years

UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1997;350:1288-1293.


Shimada A, et al. Ann N Y Acad Sci. 2003;1005:378-386.
Progression of Type 1 Diabetes
Precipitating Event

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

Adapted from DCCT Study Group. Ann Intern Med. 1998;128:517-523.


Case 6: New-onset Diabetes on CSII –
A1C Results

14.0
13.0
12.0
A1C
Case 6: New-onset Diabetes on CSII

• Patient extremely satisfied with his care


• C-peptide 0.9–0.8 at 1 year, 0.5–0.7 at 3 years
• Does not understand why everyone is not on
CSII with optimal control
Current Pump Therapy Indications

• Need to normalize blood glucose (BG)


— A1C >6.5%
— Glycemic excursions
• Hypoglycemia or hypoglycemia unawareness
• Need for a flexible insulin regimen
Summary

• Insulin remains the most powerful agent


we have to control diabetes
• When used appropriately, near-normal
glycemia can be achieved
Insulin Treatment in Type 2 Diabetes
• Basal treatment (NPH or glargine)
— Start 10 U and titrate; will need ~0.5 U/kg;
will lower A1C 1.5–2 points
• Bolus treatment premeal
— Start at 4–5 U premeal and titrate;
will lower A1C 2+ points
• Premixed therapy
— Start at 5–6 U BID and titrate; will need ~0.8 U/kg;
will lower A1C 2+ points
• Basal bolus therapy
— Start at 0.4–0.5 U/kg, 40-50% basal, 20% bolus
each meal with supplement = (BG-100) / CF
where CF = 1700/TDD
Indications for Basal Bolus Therapy
(MDI or Insulin Pump)

• All Type 1 DM patients


• All Type 2 DM patients not at goal (<6.5%)
• All hospital patients not at goal (<140 mg/dL)
• All pregnancy patients not at goal
(fasting <90 mg/dL; 1-hr PC <120 mg/dL)
Questions

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