1. Insulin Therapy Case Studies
Bruce W. Bode, MD, FACE
Atlanta Diabetes Associates Atlanta, Georgia

2. 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

3. 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

4. Case 1: Poorly Controlled Type 2 Diabetes on No Treatment
What is your goal for glucose?
90 to 130 mg/dL premeal, <180 mg/dL postmeal
80 to 110 mg/dL premeal, <140 mg/dL postmeal
70 to 100 mg/dL premeal, <120 mg/dL postmeal
ARS QUESTION

5. Case 1: Poorly Controlled Type 2 Diabetes on No Treatment
What is your treatment in addition to diet and exercise?
One oral agent
Two oral agents
Basal insulin
Premixed insulin
Basal bolus therapy
ARS QUESTION

6. 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

7. 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

8. 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?
Basal insulin morning (~10 U)
Premixed insulin morning (~10 U)
Premixed insulin morning and evening (~5 U BID)
Bolus insulin with the largest meal (~5 U)
Starch blocker or glinide (repaglinide or nateglinide)
ARS QUESTION

9. Case 2: Poorly Controlled Type 2 Diabetes on OHA 4
Case 2: Poorly Controlled Type 2 Diabetes on OHA 4. Bolus insulin with the largest meal (~6 U)

10. Case 2: Poorly Controlled Type 2 Diabetes on OHA 4
Case 2: Poorly Controlled Type 2 Diabetes on OHA 4. Bolus insulin with the am and pm meals

11. Basal/Bolus Treatment Program with Rapid-acting and Long-acting Analogs
Breakfast
Lunch
Dinner
Aspart,
Lispro Or
Glulisine
Aspart,
Lispro Or
Glulisine
Aspart,
Lispro Or
Glulisine
Plasma Insulin
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.

12. Inhaled Insulin vs Rosiglitazone in DM–2 Patients on Diet Alone
A1C, %
1.8-kg Weight Gain
0.8-kg Weight Gain
Defronzo R, et al. Accepted for publication. Diabetes Care

13. Insulin Aspart Premeal
Insulin Aspart Premeal with Metformin and Rosiglitazone vs Conventional Insulin
N=16 10
P=0.03
Baseline 9
6 months 8
A1C, % 7 6 5
Insulin Aspart Premeal
NPH or 70/30 BID
0.42 U/kg
3-kg Weight Gain
0.67 U/kg
1-kg Weight Gain
Poulsen MK, et al. Diabetes Care. 2003;26:

14. 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
Slide 6-37
INSULIN TACTICS
Starting With Basal Insulin
Advantages
Patients who no longer respond adequately to oral agents will benefit from combination therapy that consists of maintaining the use of oral antidiabetic agents together with insulin therapy. The advantages of adding basal insulin to prior treatment with oral agents include the following: (1) only one insulin injection may be required each day, with no need for mixing different types of insulin; (2) the use of insulin pens can enhance patient acceptance of the treatment; (3) titration can be accomplished in a slow, safe, simple fashion; and (4) eventually combination therapy requires a lower total dose of insulin. The result is effective improvement in glycemic control while causing only limited weight gain.

15. 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

16. 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

17. 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

18. Case 3: Poorly Controlled Type 2 Diabetes on OHA 4
Case 3: Poorly Controlled Type 2 Diabetes on OHA 4. Analog Premixed Insulin

19. 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
Time (wk)
Baseline
End Point
*Sulfonylurea + metformin
OAD=oral antidiabetic drug
Janka HU, et al. Diabetes Care. 2005;28:

20. Insulin Glargine Plus OADs vs Twice-daily Premixed Human Insulin
Change in A1C from Baseline to Study End Point*
P=0.0003
Baseline
24 week
A1C
At 24 weeks, superior reduction was achieved with insulin glargine plus OADs compared with twice-daily pre-mixed insulin.
*Intent-to-treat analysis
OAD=oral antidiabetic drug
Janka HU, et al. Diabetes Care. 2005;28:
Janka H, Plewe G, Kliebe-Frisch C, et al. Starting insulin for type 2 diabetes with insulin glargine added to oral agents vs twice-daily premixed insulin alone. Presented at: American Diabetes Association 64th Scientific Sessions; June 4-8, 2004; Orlando, Fla.

21. Documented Hypoglycemic Episodes Per Patient-Year
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
Per
Patient-Year 6 4
4.1
At 24 weeks, less hypoglycemia was documented with insulin glargine plus oral anti-diabetic drugs versus twice-daily pre-mixed insulin. 2
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:
Janka H, Plewe G, Kliebe-Frisch C, et al. Starting insulin for type 2 diabetes with insulin glargine added to oral agents vs twice-daily premixed insulin alone. Presented at: American Diabetes Association 64th Scientific Sessions; June 4-8, 2004; Orlando, Fla.

22. The INITIATE study: Analog Mix 70/30 (BID) vs glargine (QD)
Type 2 DM
BMI ≤ 40 kg/m2 Body weight ≤125 kg
HbA1C  8.0%
on metformin +/- TZD
Glargine OD (10 U, bedtime) + metformin +/- TZD
Titrate to 80 to 110 mg/dL
NovoMix® 30, pre-breakfast (5 or 6U) and pre-dinner (5 or 6U) + metformin +/- TZD
4 wk run-in:
Stop insulin secretagogues and -glucosidase inhibitors
Optimize metformin to ≥1500 mg/day
Switch rosiglitazone for 30 mg pioglitazone
The safety and efficacy of twice-daily NovoMix 30 (prebreakfast and presupper) were compared to bedtime glargine in patients with type 2 diabetes, inadequately controlled on oral antidiabetic (OAD) agents.
This randomized, 28-week, open-label, parallel-group study enrolled 233 insulin-naive patients with A1C values 8.0%, on 1000 mg/day metformin, alone or in combination with other OADs.
At baseline, patient characteristics, prior OAD treatment, demographics, and A1C values were similar between treatment groups.
(Weeks)
Raskin P, et al. Diabetes Care. 2005;28:260-65

23. Change in A1C From Baseline to Study End Point*
Glargine vs Twice-daily Analog mix 70/30 Insulin with Metformin ± Pioglitazone
Change in A1C From Baseline to Study End Point*
9.8
Baseline
9.7
P <0.01
9.8
9.7
28 week 9 8
A1C
7.4 7
6.9
At 24 weeks, superior reduction was achieved with insulin glargine plus OADs compared with twice-daily pre-mixed insulin. 6 5
Insulin Glargine + OAD
Premixed + OAD
Raskin P, et al. Diabetes Care. 2005;28:
Janka H, Plewe G, Kliebe-Frisch C, et al. Starting insulin for type 2 diabetes with insulin glargine added to oral agents vs twice-daily premixed insulin alone. Presented at: American Diabetes Association 64th Scientific Sessions; June 4-8, 2004; Orlando, Fla.

24. INITIATE 8-Pt BG Profiles - Baseline and Wk 28
350
350
BIAsp 30
Glargine
300
300
Baseline
250
250
Blood Glucose (mg/dl)
200
200 * * * + *
150
150
Week 28
100
100 50 50 BB
D90
Bed
3am
L90 BD
B90 BL
 BIAsp 70/30 lower BG vs glargine p< Glargine lower BG vs BIAsp 70/30, p<0.05
Raskin P, et al. Diabetes Care. 2005;28:

25. INITIATE – Rate of Overall Hypoglycemia (events per patient-year)
BIAsp 30
Glargine
P value
All hypoglycemia N (subjects) Mean rate
± 17.1
± 11.4
<0.05
Minor hypoglycemia N (subjects) Mean rate
± 6.6
± 2.0
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:

26. 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

27. 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

28. 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?
Change to analog mix BID
Add bolus insulin to largest meal
Add bolus insulin to each meal
Insulin pump therapy
ARS QUESTION

29. 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

30. Case 4: Poorly Controlled Type 2 on Lantus

31. 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

32. Case 5: Poorly Controlled Type 2 DM on MDI

33. 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

34. Case 5: Poorly Controlled Type 2 Diabetes on MDI
What treatment now?
Gastric bypass
Atkins diet
Find another doctor
Trial with insulin pump therapy
ARS QUESTION

35. 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

36. Case 5: Poorly Controlled Type 2 DM on MDI

37. Case 5: Poorly Controlled Type 2 Diabetes on MDI
Follow-up 3 months postpump start:
A1C 9%
SMBG 3.1/d

38. CSII vs MDI in DM 2 Patients
Less pain
Fewer social limitations
Preference
Advocacy
Less hassle
Less life interference
General satisfaction
Flexibility
Figure 2. Change-from-baseline improvements in patient satisfaction subscores at end of study. Improvements were compared between treatment groups, controlling for patient age. Responses to baseline questionnaires are based on prestudy insulin treatment. Change-from-baseline scores are available for 52 (79%) subjects in the CSII group and 52 (85%) subjects in the MDI group. Scoring of satisfaction categories ranged from 0 to 100, for least satisfaction to most satisfaction, respectively. P-values: * p<0.025, ** p<0.01, and *** p<0.001.
Convenience
Less burden -5 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

39. 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.

40. 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: 5 h
I need it, hopefully you will ok this, I won’t spend much time

41. 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

42. Case 6: New-onset Diabetes
What type of diabetes does he have?
Type 1
Type 1.5
LADA
Type 2
1, 2, or 3
ARS QUESTION

43. Case 6: New-onset Diabetes
What other diagnostic tests do you need?
Islet-cell antibody panel (ICA, anti-GAD)
Serum C-peptide
Insulin level
HLA typing
ARS QUESTION

44. 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
The antibodies which cause beta cell death are distinct from those that destroy beta cells in type 1 diabetes.
UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1997;350:
Shimada A, et al. Ann N Y Acad Sci. 2003;1005:

45. Progression of Type 1 Diabetes
Precipitating Event
Genetic
predisposition
Antibody
Progressive loss
of insulin release
Normal insulin
release
Overt diabetes
Glucose
normal
Beta-cell
mass
C-peptide
present
No C-peptide
present
Age (y)
Adapted from: Atkinson. Lancet. 2002;358:

46. 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?
IV insulin
Premixed
Basal/bolus therapy by MDI
Insulin pump therapy
ARS QUESTION

47. Options in Insulin Therapy for Type 1 Diabetes
Current
Multiple injections
Insulin pump (CSII)

48. Development of Retinopathy Rate Per 100 Patient-Years
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%
Mean A1C
10% 9% 20 20 16 16
Rate Per 100 Patient-Years 12 12
Mean A1C 8%
DCCT Absolute Risk of Retinopathy: Conventional vs Intensive Insulin Therapy 9% 8 8 7% 4 4 8% 7% 6% 1 2 3 4 5 6 7 8 9 1 2 3 4 5 6 7 8 9
Time During Study (y)
DCCT Research Group. Diabetes. 1995;44:

49. Does Intensive Insulin Therapy Preserves Beta Cell Function
1.0
0.9
0.8
0.7
Patient Probability of Maintaining C-peptide >2.0
0.6
0.5
0.4
0.3
Intensive therapy
0.2
0.1
Conventional
therapy
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
Adapted from DCCT Study Group. Ann Intern Med. 1998;128:

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

51. 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

52. 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

53. Summary
Insulin remains the most powerful agent we have to control diabetes
When used appropriately, near-normal glycemia can be achieved

54. 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

55. 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)

56. For a copy or viewing of these slides, go to: www.adaendo.com
Questions
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