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Joslin Diabetes CenterAdvances in Diabetes and Thyroid Disease 2013Pediatric Diabetes: Realistic Expectations in the 21st Century
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express writtenpermission of Joslin Diabetes Center is prohibited.
Pediatric Diabetes: Realistic Expectations is the 21st Century
Sanjeev Mehta, MD, MPH
Director of Quality, Joslin Diabetes Center
Staff Physician, Pediatric, Adolescent, and Young Adult Section
Assistant Investigator, Genetics and Epidemiology Section
Disclosure Statement
I have no financial disclosures.
Pediatric Diabetes: Lecture Overview
Epidemiology: Incidence / Prevalence
Diagnostic criteria
Glycemic outcomes
Intensive diabetes management• Blood glucose (BG) monitoring
• Nutrition and meal planning
• Insulin regimens
• Continuous glucose monitoring (CGM)
Comorbidities
Abbreviations: type 1 diabetes (“T1D”), type 2 diabetes (“T2D”)
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Joslin Diabetes CenterAdvances in Diabetes and Thyroid Disease 2013Pediatric Diabetes: Realistic Expectations in the 21st Century
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express writtenpermission of Joslin Diabetes Center is prohibited.
Q1: In the US, what percentage of African American or Hispanic youth aged <10 years with new-onset diabetes will have type 2 diabetes?
1. 50%
2. 25%
3. 10%
4. 5%
Epidemiology of Pediatric Diabetes
Incidence: 15,000 T1D/yr vs. 3,700 T2D/yr
Prevalence*: 215,000 youth with diabetes
Age at diagnosis• ~75% T1D diagnosed at age <18 years old
• The majority of people with T1D are adults
• Majority of T2D is diagnosed in adults
Female to male ratio: 1 in T1D vs. 1.6 in T2D
Race / Ethnicity • T1D more common in non-Hispanic whites
• T2D more common in minority groups
*2010
Incidence (United States)
2,435 youth <20 years with newly diagnosed diabetes between 2002–2003 (10 locations)
78% T1D and 22% T2D
Writing Group for the SEARCH for Diabetes in Youth Study. JAMA. 2007;297:2716-2724.
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Joslin Diabetes CenterAdvances in Diabetes and Thyroid Disease 2013Pediatric Diabetes: Realistic Expectations in the 21st Century
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express writtenpermission of Joslin Diabetes Center is prohibited.
Incidence (Finland)
10,737 youth <15 years diagnosed diabetes between 1980-2005
Incidence (per 100,000/yr) more than doubled from 31.4 in 1980 to 64.2 in 2005 (US ~25)
The rise in incidence was greatest among young children ages 0-4 years
Conclusions• Number of new cases diagnosed <14 years of age
will double again in the next 15 years
• Age of onset will be younger (0-4 years)
Harjutsalo, Lancet 2008; 371: 1777-82
Incidence (Finland)
Recent evidence suggests possible plateau following rapid rise in incidence...too early?
Harjutsalo, Lancet 2008; 371: 1777-82Harjutsalo, JAMA 2013; 310: 427-428
2008 2013
Prevalence (United States)
154,369 youth age <20 years with diabetes in the US; overall prevalence was 0.18%
0-9 years 10-19 years
SEARCH for Diabetes in Youth Study Group. Pediatrics. 2006;118:1510-1518.
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Joslin Diabetes CenterAdvances in Diabetes and Thyroid Disease 2013Pediatric Diabetes: Realistic Expectations in the 21st Century
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express writtenpermission of Joslin Diabetes Center is prohibited.
ADA Diagnostic Criteria
Prediabetes• Impaired fasting glucose (IFG): ≥100 and <126
mg/dL• Impaired glucose tolerance (IGT): 2-hour blood
glucose during OGTT ≥140 and <200 mg/dL
Diabetes• Fasting blood glucose ≥126 mg/dL• 2-hour blood glucose during OGTT ≥200 mg/dL• Random blood glucose ≥200 mg/dL associated with
polydipsia, polyuria, and/or weight loss• Hemoglobin A1c ≥6.5% on two occasions
American Diabetes Association. Diabetes Care. 2009; 32:S62-S67. Diabetes Care. 2009;32:1327-1334.
Differentiating Pediatric T1D and T2DType 1 Diabetes Type 2 Diabetes
Diagnosis age<10; Caucasians if age at diagnosis >10 years
Racial/ethnic minority and age at diagnosis >10 years
Not usually overweight; proportionate to obesity in general population
85% are overweight
35-40% present with ketoacidosis 33% with ketonuria;5-25% may have ketoacidosis
5% with a 1st- or 2nd-degree relative with T1D
74-100% with 1st- or 2nd-degree relative with T2D
Increased incidence of other autoimmune diseases
Increase in PCOS; acanthosisnigricans (up to 90%)
Decreased c-peptide and insulin;no increase with glucose challenge
Normal or increased c-peptide and insulin; increased with glucose challenge
Goals of Pediatric Diabetes Management
Utilize intensive therapy aimed at near-normal BG and hemoglobin A1c levels
Prevent diabetic ketoacidosis and severe hypoglycemia
Achieve the highest quality of life compatible with the daily demands of diabetes management
In children, achieve normal growth and physical development and psychological maturation
Establish realistic goals adapted to each individual’s circumstances
ADA Standards of Care 2013.ADA Position Statement. Care of children with diabetes, 2005;28:186–212, updated 2012.
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Joslin Diabetes CenterAdvances in Diabetes and Thyroid Disease 2013Pediatric Diabetes: Realistic Expectations in the 21st Century
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express writtenpermission of Joslin Diabetes Center is prohibited.
AdultsAdolescents
Reichard P et al. N Engl J Med. 1993;329:304-309. DCCT Research Group. J Pediatr. 1994;125:177-188.
Diabetes Control and Complications Trial: Adult and Adolescent Cohorts
Risk of Retinopathy Progression
A1c 10% x 3 yearsvs.
A1c 8% x 8 years
JAMA. 2002:287.
DCCT Research Group. J Pediatr. 1994;125:177-188.DCCT/EDIC Research Group. J Pediatr. 2001; 139: 804-12.
Benefits of Intensive Diabetes Therapy during Adolescence (DCCT/EDIC)
Intensive diabetes management:• improved A1c compared to conventional therapy
• reduced the risk of diabetic eye disease by 53-70%
• reduced the risk of diabetic kidney disease by 55%
Blood glucose monitoring played a major role in intensive therapy, allowing for optimal insulin dosing
Newer insulins and advanced technologies can aid in the achievement of target blood glucose and A1c levels
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Joslin Diabetes CenterAdvances in Diabetes and Thyroid Disease 2013Pediatric Diabetes: Realistic Expectations in the 21st Century
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express writtenpermission of Joslin Diabetes Center is prohibited.
Maintenance of C-Peptide Production with Intensive Therapy (DCCT)
DCCT
Ann Intern Med. 1998;128:517-523.
DCCT: Risk of hypoglycemia as A1c
Reichard P et al. N Engl J Med. 1993;329:304-309.
DCCT (1993): Adolescents (vs Adults)
Significantly higher A1C levels• Intensive 8.1 vs 7.1%
• Conventional 9.8 vs 9.0%
Significantly more hypoglycemia• Intensive 86 vs 57/100 pt-yrs
• Conventional 28 vs 17/100 pt-yrs
Significantly more diabetic ketoacidosis (DKA)• Intensive 2.8 vs 1.8/100 pt-yrs
• Conventional 4.7 vs 1.3/100 pt-yrs
Reichard P et al. N Engl J Med. 1993;329:304-309. Diabetes Control and Complications Trial Research Group. J Pediatr. 1994;125:177-188.
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Joslin Diabetes CenterAdvances in Diabetes and Thyroid Disease 2013Pediatric Diabetes: Realistic Expectations in the 21st Century
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express writtenpermission of Joslin Diabetes Center is prohibited.
Incidence of SH, DKA in Current Era
Incidence of severe hypoglycemia (SH)*
Incidence of DKA*
Rewers et al. JAMA. 2002;287(19):2511-2518; *manuscript summarizes literature on published SH, DKA rates
Overall incidence: 19/100 pt-yearsGirls: decreased with ageBoys: no association with age
Associated with psychiatric disorder,underinsured, longer duration, higher A1c
Overall incidence: 8/100 pt-yearsGirls: increased with ageBoys: no association with age
Associated with psychiatric disorder,underinsured, higher daily insulin, higher A1c
Association between A1c and severe hypoglycemia (SH) and DKA in 2013 Youth and young adults aged 2-26 years (n=13,487)
in the T1D Exchange Registry with T1D ≥ 2 years
0
5
10
15
20
25
30
35
% with ≥1 SH event % with ≥1 DKA event
% of Youth
Miller K. Diabetes Care 2013;36:2009-14.
SH frequency: highest in children <6 years old
DKA frequency: highest in adolescents
Q2: What is the average hemoglobin A1c for youth with type 1 diabetes in the US or Europe?
1. 9.4%
2. 8.6%
3. 7.7%
4. 7.2%
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Joslin Diabetes CenterAdvances in Diabetes and Thyroid Disease 2013Pediatric Diabetes: Realistic Expectations in the 21st Century
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express writtenpermission of Joslin Diabetes Center is prohibited.
Glycemic Goals in Pediatric Diabetes
“near normalization of blood glucose levels is seldom attainable...after the honeymoon”
A lower goal may be reasonable if it can be achieved without excessive hypoglycemia
Age Group A1cBlood Glucose (before meals)
Blood Glucose(Bedtime/night)
Toddlers and preschoolers(0-5 years) <8.5% 100 – 180 110 – 200
School age (6-12 years) <8.0% 90 – 180 100 – 180
Adolescents and young adults (13-19 years); ISPAD* <7.5% 90 – 130 90 – 150
Adults(≥20 years) <7.0%
ADA Position Statement. Care of Youth with diabetes, 2005;28:186–212, updated 2012*International Society for Pediatric and Adolescent Diabetes
Glycemic Control (International)
2,873 youth with T1D from 18 countries
19958.6 1.7%
20058.7 1.5%
19988.7 1.8%
4 5 6 7 8 9 10 11 12 13 14 15 16 170
5
10
15
20
25
30
% of Youth
Male Female
A1c (%)
Mortensen et al: Diabetes Care 1997; Danne et al: Diabetes Care 2001; de Beaufort et al: Diabetes Care 2007.
Glycemic Control (United States)
A1c levels for 13,487 youth and young adults participating in the T1D Exchange Clinic Registry
36
12
18
31
1614
0
5
10
15
20
25
30
35
A1c (%)
% of Youth
20138.6 1.5%
Miller K. Diabetes Care 2013;36:2009-14.
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Joslin Diabetes CenterAdvances in Diabetes and Thyroid Disease 2013Pediatric Diabetes: Realistic Expectations in the 21st Century
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express writtenpermission of Joslin Diabetes Center is prohibited.
Glycemic Control (United States)
Percent of youth (n=13,226) attaining age-specific A1c goals in the T1D Exchange Clinic Registry
% of Youth
ADA Guidelines ISPAD Guidelines
8.2 1.1% 8.3 1.2% 8.8 1.7%
Wood J. Diabetes Care 2013;36:2035-37.
Increasing BG monitoring by 2 checks daily has been associated with a 0.5% absolute reduction in A1c
Blood Glucose Monitoring and A1c
Levine BS. J Pediatr 2001;139:197–203.
n=300 youth with T1D, ages 7-16 yrs
T1D Exchange Clinic Registry (n=20,555)
Blood Glucose Monitoring and A1c
Miller K. Diabetes Care 2013;36:2009-14.
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Joslin Diabetes CenterAdvances in Diabetes and Thyroid Disease 2013Pediatric Diabetes: Realistic Expectations in the 21st Century
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express writtenpermission of Joslin Diabetes Center is prohibited.
Q3: What is the largest difference between mealtime carb estimates and actual carb amounts that will support optimal glycemic control?
1. 20-30 grams
2. 10-15 grams
3. 5-8 grams
4. 1-3 grams
*hyperglycemia or hypoglycemia
Dietary Quality in Pediatric Diabetes
SEARCH Study (89% T1D, age 10-19 yrs, n=1697)
Mayer-Davis, J Amer Diet Assoc, 106:689, 2006
Dietary Quality in Pediatric Diabetes
Children ages 2-12 years (T1D vs. NHANES*, n=67)
Mehta, unpublished. *National Health and Nutrition Examination Survey, 2005-06.
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Joslin Diabetes CenterAdvances in Diabetes and Thyroid Disease 2013Pediatric Diabetes: Realistic Expectations in the 21st Century
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express writtenpermission of Joslin Diabetes Center is prohibited.
Dietary Quality in Pediatric Diabetes
Children with T1DAges 2-12 yearsN=67, 1 center
Children with DMAges 10-19 yearsN=1697, 6 centers
Mehta, unpublished. *National Health and Nutrition Examination Survey, 2005-06. Mayer-Davis, J Amer Diet Assoc, 106:689, 2006.
Dietary Quality in Pediatric Diabetes
Summary of overall nutrition• Low intakes of fruit, vegetables, and whole grains
• Very low intakes of daily fiber
• High intakes of total and saturated fat
• Adequate intakes of protein
Stable across populations over time• Children, young adults, and adults with T1D
• United States, Europe, and Asia
• Similar findings published over the last 30 years
Carbohydrate Estimation/Counting
Limited published data on the association between carbohydrate estimation and A1c until 2009
To date, no method of carbohydrate estimation has proven superior in achieving glycemic targets
Carbohydrate counting is commonly used to calculate prandial insulin doses for intensively treated youth with diabetes
Meal estimates for meals within 10-15 grams do not appear to negatively impact glycemic control• Postprandial glucose excursions or hemoglobin A1c
• Precise (consistent) estimation may be more important than accurate estimation in optimizing hemoglobin A1c
Mehta, Diabetes Care, 32:1014, 2009 Bishop, Diabetes Spectrum, 22:56, 2009Smart, Diabetic Medicine, 26:279, 2009 Smart, Diabetic Medicine 27, 348–353 (2010)
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Joslin Diabetes CenterAdvances in Diabetes and Thyroid Disease 2013Pediatric Diabetes: Realistic Expectations in the 21st Century
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express writtenpermission of Joslin Diabetes Center is prohibited.
Patient Perspective on Healthy Foods
Focus group analysis • Youth with T1D (n=35) and their parents
• Understand perceptions of healthful eating and the impact of diabetes management
Focus group themes• Defining healthful foods
– Traditional notions (fruits, vegetables, whole grains)
– Foods which did not cause “spikes” in BGs (low carb or easy to estimate carbohydrate amount)
• Use of flexible insulin regimens– Normalcy in dietary behaviors (good and bad)
– Generally, but not always, easier than fixed regimens
Mehta, Diabetes Care, 32:2174, 2009
Patient Perspective on Healthy Foods
“It all comes back to what’s on that glucose meter…If that number’s good, then whatever we have [to eat] in the house is good.” [Parent]
“I would say [unhealthy eating] is anything he’s unable to accurately count the carbs on.” [Parent]
“Everyone wants me to eat healthy, but when I try to eat a fruit or something like that…I can’t eat it.” [Child with T1D]
Mehta, Diabetes Care, 32:2174, 2009
Patient Perspective on Healthy Foods
Mehta, ADA Scientific Sessions, 2008
Grains
Prepackaged foods
Fruits
Vegetables
Milk
Fast food
FatFiber
Sugar-sweetened
foods
Protein
HEALTHY UNHEALTHY
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Joslin Diabetes CenterAdvances in Diabetes and Thyroid Disease 2013Pediatric Diabetes: Realistic Expectations in the 21st Century
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express writtenpermission of Joslin Diabetes Center is prohibited.
Youth with T1D (US, n=2,743)
Regimen intensification was associated with better outcomes in related analysis
Insulin Regimens (SEARCH Study)
Paris, J Pediatr 2009;155:183-9Pihoker, Diabetes Care 2013; 36:27-33
Youth with T1D (Europe, n=1,133)
Acute events• DKA: no difference according to regimen
• Severe hypoglycemia (/100 pt-years)– No events in 96% of cohort
– Lowest in pump (5.4) and highest in pre-mixed (42.4)
Insulin Regimens (Hvidoere Study)
de Beaufort, Pediatric Diabetes 2013: 14: 422–428.
Insulin Pump/CSII
Basal-BolusInjection
Conventional(twice daily)
Conventional (twice+PRN)
Conventional (pre-mixed)
% Youth 32.8 16.9 36.5 7.5 6.3
A1c (%) 7.8 0.9% 8.0 1.0% 8.2 1.0% 7.3 0.5% 8.5 1.7%
Insulin Pump Use
Mehta S. Endocrinol Metab Clin N Am 2010; 39: 573–593
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Joslin Diabetes CenterAdvances in Diabetes and Thyroid Disease 2013Pediatric Diabetes: Realistic Expectations in the 21st Century
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express writtenpermission of Joslin Diabetes Center is prohibited.
Challenges of Pump Use vs Injections
53%
79%
23%
47%
0%
20%
40%
60%
80%
100%
Insulin after Eating Forgets Insulin
Pump Injections
P<0.0001 P<0.0001
Courtesy L. Laffel.
Burdick J et al. Pediatrics. 2004;113:e221-e224.
A1C increases 1% / 4 missed boluses/week
Missed Insulin Meal Boluses and A1C
A1C levels correlated with the number of missed meal insulin boluses per day (r = 0.4)
(n=48)
Potential benefits of pump therapy• Lower hemoglobin A1c (0.2-0.5%)
• Less frequent nocturnal hypoglycemia– Similar or lower rate of overall hypoglycemia
– Similar or lower rate of severe hypoglycemia
• Lower total daily insulin dose, but not weight/BMI
• Similar or better quality of life, but need additional studies comparing to flexible injection regimens
Potential risks of pump therapy• Risk of DKA (absence of long-acting insulin)
• Missed insulin boluses (and higher A1c)
Insulin Regimens
Mehta S. Endocrinol Metab Clin N Am 2010; 39: 573–593
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Joslin Diabetes CenterAdvances in Diabetes and Thyroid Disease 2013Pediatric Diabetes: Realistic Expectations in the 21st Century
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express writtenpermission of Joslin Diabetes Center is prohibited.
JDRF Continuous Glucose Monitoring Study Group, NEJM, 2008; 359.
Relationship between Change in A1C and Frequency of CGM Use
Change in A1C-0.9
-0.7
-0.5
-0.3
-0.1
0.1
Ch
ang
e in
A1C
Prevalence of CVD Risk Factors in T1D
Cardiovascular disease risk factors
US (SEARCH)
Norway (NCDQ)
Germany (DPV, F)
Germany (DPV, M)
Above A1c target (ADA)
55.6 71.4 61 59
Dyslipidemia 43.0 41.4 34 22
Obesity 12.6 4.4 23 18
Elevated BP 5.9 6.9 23 19
Microalbuminuria 9.2 1.0 N/A N/A
* Petitti, J Pediatrics, 155:668, 2009 Liu, Pediatric Diabetes, 11:4, 2010 Maahs, Diabetes Care, 30:2593, 2007Kershnar, J Pediatrics, 149:314, 2006 Rodriguez, Pediatrics, 15:245, 2010 Margeirsdottir, Diabetologia, 50:207, 2007Schwab, Pediatric Diabetes, 11:357, 2010
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Joslin Diabetes CenterAdvances in Diabetes and Thyroid Disease 2013Pediatric Diabetes: Realistic Expectations in the 21st Century
Copyright © 2013 by Joslin Diabetes Center, Inc. All rights reserved. These materials may be used for personal use only. Any distribution or reuse of this presentation or any part of it in any form for other than personal use without the express writtenpermission of Joslin Diabetes Center is prohibited.
Prevalence of CVD Risk Factors in T1D
Number of CVD risk factors
Number of CVD risk factors
Norway (NCDQ)n=576
Germany (DPV)n=33,488
0 14.0 26.0
1 41.0 39.0
2 30.0 24.3
3 12.6 8.7
≥4 2.4 2.0
* Margeirsdottir, Diabetologia, 50:207, 2007Schwab, Pediatric Diabetes, 11:357, 2010
Joslin Medalists
Awarded to individuals with physician-confirmed insulin dependence for ≥25 years
25-Year
(1948)
50-Year
(1970)
75-Year
(1995)
80-Year
(2013)
Pediatric Diabetes: Realistic Expectations is the 21st Century
Sanjeev Mehta, MD, MPH
Director of Quality, Joslin Diabetes Center
Staff Physician, Pediatric, Adolescent, and Young Adult Section
Assistant Investigator, Genetics and Epidemiology Section
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