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

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

Type 1 Diabetes Mellitus Autoimmune Disease

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

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

T1D incidence is rising 3-5% per year

Normal Skin Acanthosis Nigricans Hyperkeratosis Papillomatosis

Maturity Onset Diabetes of the Young (MODY)

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

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®)

Insulin Preparations Regular Insulin

Insulin Preparations Regular Insulin Analog Insulin

Analog Insulin

Insulin Preparations NPH

Glargine (Lantus®)

Glargine (Lantus®)

Intra-subject Variability Insulin Glargine 32 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). -1 4 9 14 19 24 -1 4 9 14 19 24 -1 4 9 14 19 24 -1 4 9 14 19 24 Time [h] Visit 2 Visit 3 Scholtz et al. Diabetes 1999;48(suppl 1):A97. Abst 416; Study 1012

Levemir

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

Insulin Levels After NPH Injection Child Adolescent Adult Insulin Level 0 3 6 9 12 15 18 21 24 Elapsed time (hours)

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

Injection Technique

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

Increased Subcutaneous Blood Flow

What Does Insulin Do?

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

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

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

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

Insulin Regimens

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

3 injections per day Analog and Lantus B L D

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

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

Insulin Pens

Insulin Pumps Subcutaneous Insulin Infusion (SCII)

Insulin Pump with Analog Insulin B L D

Insulin Pump Therapy

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

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

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

100 40 200 Insulin Adrenaline Cortisol Growth Hormone Glucagon

Exercise 100 40 200 Adrenaline Insulin Cortisol Glucagon Growth Hormone Glucagon

Glucose Monitoring

Interstitial Glucose

Continuous Glucose Sensors Guardian Navigator Dexcom

Type 2 DM Pathophysiology

Type 2 DM Treatment

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