5/16/2018 1 PHIL ZEITLER MD, PHD SECTION OF ENDOCRINOLOGY DEPARTMENT OF PEDIATRICS UNIVERSITY OF COLORADO DEPARTMENT OF ENDOCRINOLOGY CHILDREN’S HOSPITAL COLORADO Pediatric Case Studies Blake 15 yo NHW male with long history of overweight and two year increase in weight gain Denies change in eating or activity habits Small breakfast, school lunch, “large” dinner Fast food once a week PE at school every day 4-5 hours/day of screen time No medications. Depakote two years ago (one year) ROS: daytime sleepiness, snoring. Otherwise negative Blake Past Hx: Uncomplicated pregnancy, BW 5lbs 12 oz, no GDM Asperger’s syndrome Fam Hx: Paternal grandmother with T2DM Father with elevated cholesterol Mat uncle with HTN, MI at 45, elevated cholesterol Maternal GF with MI at 61, HTN, elevated cholesterol
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Pediatric Case Studies - professional.diabetes.org · Pediatric Case Studies ... pediatric endocrinologist for screening, 119 (9.8%) were positive for diabetes autoimmunity Klingensmith
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5/16/2018
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PHIL ZEITLER MD, PHD
SECTION OF ENDOCRINOLOGY
DEPARTMENT OF PEDIATRICS
UNIVERSITY OF COLORADO
DEPARTMENT OF ENDOCRINOLOGY
CHILDREN’S HOSPITAL COLORADO
Pediatric Case Studies
Blake
15 yo NHW male with long history of overweight and two year increase in weight gain
Denies change in eating or activity habits Small breakfast, school lunch, “large” dinner
At least 9.8% of US youth identified with T2D by pediatric endocrinologists on clinical grounds are antibody positive some potential subjects were prescreened for DAA
insulin auto-antibodies were not measured
anti ZnT8 (and other unknown antibodies were not measured)
Although antibody positive youth with diabetes are clearly different from antibody negative youth, antibody positive youth are clinically indistinguishable from antibody negative youth
Youth who were ZnT8 positive or who converted to GAD positivity had more rapid loss of glycemic control
Antibody measurement should be considered in obese youth diagnosed with type 2 diabetes
Klingensmith et al Diabetes Care 2010
Non-glycemic evaluation at diagnosis
Blood pressure
(Fasting) lipid panel
AAP: lipid panel between 7-10 and after completion of puberty
Presence of fatty liver
ALT/AST, though low sensitivity
Urine albumin/creatinine ratio
Depression screening
Evaluation for sleep disturbance
Evaluation for PCOS in females
Birth control counseling
Dental evaluation
Burden of family illness
Zeitler et al Pediatr diabetes 2014
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Ongoing screening
HbA1c every 3-4 months
BP – every visit
Lipid panel: annual
Foot exam/MNSI/monofilament testing – annual
Eye exam – annual/every 2 years
Dental cleaning and exam – every 6 months
Sleep apnea screen every visit
? Vitamin D
Depression screen: every visit
Zeitler et al Pediatr diabetes 2014
Katz et al Diabetes Care. 2016
Depression in youth-onset type 2
Depression is common in US youth with type 2 diabetes, though not at higher rates than obese youth without diabetes
A greater percentage of participants with low adherence had clinically significant depressive symptoms at baseline (18% vs. 12%)
The odds of medication nonadherence increased significantly from those reporting ≥ 1 major life stressor (OR 1.58) to those reporting ≥ 4 major life stressors (OR 2.70)
Significant odds of elevated depressive symptoms and impaired QoL were also found with increased reporting of major stressors
Larkin et al Diabetes Manag (Lond). 2015
Depression and quality of life
At baseline, 22.2% of participants demonstrated impaired HRQOL
Depressive symptoms distinguished those with impaired HRQOL and were significantly related to later impaired HRQOL
Other comorbidities did not have a significant impact on HRQOL
Physical Health Psychological Health
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Arturo
15 yo Latino male with fasting glucose of 289 mg/dL (16 mmol/L) at yearly exam
BMI 32 Kg/M2, BP 120/65, Tanner 5.
Antibodies (GAD, IA2, ZnT8, mIAA) negative
Of the following, what hemoglobin A1c would you use to decide to start insulin:
A. I would always start insulin
B. 6.5%
C. 7.5%
D. 8.5%
E. 10%
A1c < 8.5%* A1c > 8.5%No Acidosis with or without ketosis
Acidosisand/or DKA
and/or HHNK
•metformin PO bid•Titrate up to 2000 mg per day as tolerated
•basal insulin: start at 0.5 U/kg/day and escalate every 2-3 days based on meter glucose•metformin
•titrate up to 2000 mg per day as tolerated
•Manage DKA or HHNK•IV insulin until acidosis resolves, then subcutaneous
Pancreatic autoantibodies
Continue metforminwean insulin
A1C goals not met
Initiate or continue add-on insulin therapy - basal insulin to max 1.5 unit/kg/day
Continue or initiate MDI insulin therapy
positivenegative
A1C Goals Not Met
New Onset Diabetes in Overweight Youth
Consider other drug therapy
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Arturo
15 yo Latino male with fasting glucose of 289 mg/dL (16 mmol/L) at yearly exam
BMI 32 Kg/M2, BP 120/65, Tanner 5.
HbA1c 8.7%
You start him on metformin and titrate to 2000 mg a day
He returns in 3 months
HbA1c is 7.0%
He and his mom report good adherence to metformin
Of the following, the BEST next step in management is:
A. Make no changes - patient is at target
B. Start basal insulin
C. Start GLP-1 agonist
D. Start sulfonylurea
E. Start thiazolidinedione
At diagnosis:
Lifestyle+
Metformin
Lifestyle + Metformin+
Basal insulin
Lifestyle + Metformin+
basal insulin+?
>6.5%
Pathophysiology – based treatment algorithm for Pediatric Type 2 diabetes
Metformin intoleranceSevere resistance
TZD
ObesityGLP-1 agonist
Off label
Obesity/hypertensionDKD
SGLT2 inhibitor
Aggressive Disease: Early
Combination therapy?
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Effect of insulin on glycemic and non-glycemic outcomes
No difference in HbA1c 1 year after starting insulin
At failure
9.7 ± 1.7%
1 year later
9.5 ± 2.0%
Insulin improves but does not correct dyslipidemia or inflammatory status
Levitt Kat et al J Pediatr 2018
Anthony
T2D 4 years ago metformin 2000 mg - 4 years
glargine insulin 110 units – 2.5 years
liraglutide 1.8 mg - 1 year
BP 138/92
HbA1c 8.6%
AST 85 U/L (1.42 µkat/L), ALT 110 U/L (1.84 µkat/L)
Fasting triglycerides 320 mg/dL (3.62 mmol/L)
LDL 160 mg/dL (4.14 mmol/L)
Urine albumin/creatinine 40
Of the following, what would be the MOST important next step in management?