1. Diabetes Update: Michael Gottschalk, M.D, Ph.D.
Department of Pediatrics
University of California, San Diego

2. Diabetes Mellitus Type 1 70-80 % Type 2 20-25% MODY 1-2% Autoimmune
Insulin resistance
Insulin deficiency
MODY %
Monogenic disorder

3. Type 1 Diabetes Mellitus
Autoimmune Disease

4. Chromosome 6 High risk genotype HLA complex Regulate immune response
HLA-DR3, HLA-DR 4,
HLA-DR3/4

5. Etiology of Type 1 Diabetes Mellitus
Genetics
Risk of developing T1DM
Environment
Trigger for developing T1DM

7. T1D incidence is rising 3-5% per year

9. Normal Skin
Acanthosis Nigricans
Hyperkeratosis
Papillomatosis

11. Maturity Onset Diabetes of the Young (MODY)

12. Diabetes Medical Management Plan
Diabetes in School
Diabetes Medical Management Plan
Insulin
Meals
Exercise
Hypoglycemia
Hyperglycemia
Ketone testing

13. Insulin Products Regular Insulin Analogue Insulin NPH Insulin
Glulisine (Apidra®)
Lispro (Humalog®)
Aspart (Novolog®)
NPH Insulin
Combination
Novolog® Mix 70/30
Humalog® Mix 75/25
Novolin® 70/30
Long-Acting Insulin
Glargine (Lantus®)
Determir (Levemir®)

15. Insulin Preparations
Regular Insulin

16. Insulin Preparations
Regular Insulin
Analog Insulin

18. Analog Insulin

19. Insulin Preparations
NPH

22. Glargine (Lantus®)

23. Glargine (Lantus®)

24. Intra-subject Variability Insulin Glargine32 24 16 8 32 24 16 8
Subject 14
Subject 18
Subject 19
Subject 22
Concentrations [mlU/mL] 32 24 16 8
Subject 27
Subject 28
Subject 34
Subject 35
PK/PD of Insulin Glargine
Intra-Subject Variability of Action
This slide shows insulin glargine activity after two injections (7-day washout period between injections) in 12 healthy male subjects (Study 1012).
Time [h]
Visit 2
Visit 3
Scholtz et al. Diabetes 1999;48(suppl 1):A97. Abst 416; Study 1012

25. Levemir

26. Insulin Variability Preparation Size of the Injection
Injection Technique
Injection Site
Subcutaneous blood flow

27. Insulin Levels After NPH Injection
Child
Adolescent
Adult
Insulin Level
Elapsed time (hours)

28. Size of the Injection Larger size of the dose
Variability in absorption is increased
Total amount absorbed is decreased

29. Injection
Technique

30. Site of injection Abdomen is fastest Arm is intermediate
Legs and buttock are
the slowest

31. Increased Subcutaneous Blood Flow

32. What Does Insulin Do?

33. Normal glucose metabolism+
Skeletal Muscle
Liver
Glucose +
Fat
Pancreas
Insulin
Glucose and other nutrients
GI Tract
Adapted from Cell, Vol 97, 9-12

34. Normal glucose metabolism Fasting
Brain
Ketone bodies +
Free fatty acids +
Skeletal Muscle
Liver
Fat
Glucose
Pancreas
Adapted from Cell, Vol 97, 9-12

35. Normal glucose metabolism−
Brain
Ketone bodies −
Amino acids −
Triglyceride +
Free fatty acids −
Skeletal Muscle
Liver
Glucose +
Fat
Pancreas
Insulin
Glucose and other nutrients
GI Tract
Adapted from Cell, Vol 97, 9-12

36. Insulin BASAL AND BOLUS
Regulate hepatic glucose production
Prevent ketone production
Equivalent to ~ ½ of daily insulin requirement
Bolus:
Prevent postprandial hyperglycemia

37. Insulin Regimens

38. 2 injections per day
Regular and NPH
Reg/NPH Reg/NPH
B sn L sn D sn

39. 3 injections per day
Analog and Lantus
B L D

40. 3 injections per day Analog and Lantus Analog Analog Analog Lantus
B L D

41. 2 injections per day Humalog/Novolog, Lantus and NPN
Analog Analog
NPH Lantus
B L D

42. Insulin Pens

43. Insulin Pumps Subcutaneous Insulin Infusion (SCII)

44. Insulin Pump with
Analog Insulin
B L D

45. Insulin Pump Therapy

46. CSII vs MDI Lower HbA1c Lower prevalence of severe hypoglycemia
0.5% improvement
Lower prevalence of severe hypoglycemia
60-70% reduction
Less glucose variability

47. Exercise and Glucose Normal glucose (70 – 120) “The Goal”
Hypoglycemia (Low glucose)
Lack of carbohydrate
Insulin excess
Increased insulin sensitivity
Muscle glucose uptake independent
of insulin
Hyperglycemia (High glucose)
Excess carbohydrate
Insulin deficiency
Stress/Nervousness

48. Exercise Intensity Moderate - Sustained High - Short Duration Aerobic
Tend to cause low glucose
Activities:
Running
Cycling
Swimming
Soccer
High - Short Duration
Anaerobic
Tend to cause high glucose
Activities:
Sprinting
Power lifting
Hockey

49. 100 40
200
Insulin
Adrenaline
Cortisol
Growth Hormone
Glucagon

50. Exercise 100 40 200 Adrenaline Insulin Cortisol Glucagon
Growth Hormone
Glucagon

51. Glucose Monitoring

52. Interstitial Glucose

53. Continuous Glucose Sensors
Guardian
Navigator
Dexcom

56. Type 2 DM Pathophysiology

57. Type 2 DM Treatment

59. Where Should Diabetes Care Be Provided?
Diabetes care should be provided wherever your child is on campus, on the school bus, and at off-campus activities.
If the parent requests it and the treating physician authorizes it, the child will be permitted to check his or her blood glucose level and to otherwise provide diabetes self-care in the:
classroom,
in any area of the school or school grounds,
during any school-related activity,
upon specific request by the parent, in a private location