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Growth (Short Stature, Obesity)Diabetes Mellitus in Children
Sioksoan Chan-Cua, MDAssociate Professor
Pediatric Endocrinologist
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Learning Outcomes
Short stature• Identify causes of short stature• Acquire skill in history-taking, physical
examination in a child with short stature• Diagnose pathologic short stature• Propose diagnostic work-ups • Provide treatment plan
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Growth - Height
• Normal growth• Short stature
– Causes
• Diagnosis – history and physical examination– work-up– treatment / management plan
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Growth Rate Through Adolescence
Girls (11 yr) 6 - 11 cm 2.5 - 4.5 inBoys (13 yr) 7 - 13 cm 3 - 5 in
Birth to 1 year:
18 - 25 cm (7 - 10 inches )
1 to 2 years:10 to 13 cm (4 to 5 inches)
2 years to pre-puberty :
5 to 6 cm (2 to 2.5 inches)
Puberty:
At birth, full-term baby’s Length: 50 cm (20 in )Weight: 3 kg (7 lb)
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DEFINITIONS
• SHORT STATURE– Height < 3rd percentile for
age
• GROWTH FAILURE– Growth rate < 5 cm/year
after age 2 years
Short Stature with Slow Growth Rate
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Factors Affecting Growth
• Nutrition (malnutrition)• Diseases (chronic diseases)• Genes/ heredity• Hormones• Psychological factors
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Genetic Control of Growth • Chromosomes
– Abnormalities – missing, or trisomy
• Genes– normal development & function of the pituitary – growth hormone / insulin-like growth factor axis
– Mutations of these genes • responsible for abnormal growth
– Growth hormone deficiency• GHD IA: AR, complete GH-1 gene deletion• GHD IB: AR, point mutation• GHD II: AD• GHD III: x-linked inheritance
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Pituitary-specific transcription factors• Play a role in determination of pituitary cell lineages
Rpx (Hesx1) differentiation of pituitary (eg. SOD)
Ptx (Pitx/ P-OTX) Present in fetal and adult pituitaryPtx 2 is expressed in the somatotrophs (S), lactotrophs (L), thyrotrophs (T) & gonadotrophs
Lhx3 (LIM-3/ P-Lim) maintenance function
PROP – 1 required for S, L, T determination
Pit-1 (GHF-1, POU1F1)
development of S, L, Tcell-specific gene expression and regulation
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Hormones Affecting Growth
1. Growth hormone (GH)
2. Thyroid hormone
3. Glucocorticoids
4. Sex hormones
5. Insulin – important fetal growth factor(infant of diabetic mother is macrosomic)
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Hormonal Control of GrowthPituitary Gland and GH
GH is a protein with 191 amino acids and its secretion is pulsatile. GH may be influenced by ghrelin levels in the hypothalamic-pituitary portal circulation and the systemic circulation
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Causes of Short Stature
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Familial Short Stature
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FAMILIAL SHORT STATURE
• Growth may be reduced between 6 & 18 months then growth becomes steady but below the 5th P
• No weight deficits for height and no bone age delay (BA = CA)
• TREATMENT: – None– Long term GH results in very modest height increase
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Constitutional Growth Delay
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CONSTITUTIONAL GROWTH DELAY
• A common cause of short stature & sexual infantilism in the adolescent
• Normal growth progression paralleling a lower percentile curve until catch up growth occurs
• Usually occurs in boys; occurs occasionally in girls • (+) family history
• TREATMENT: – Reassurance– Testosterone only if BA > 12 years for 4-6 months
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CAUSES of SHORT STATURE
PATHOLOGICAL • Disproportionate
– Bone development disorders (Skeletal dysplasia)
• Achondroplasia• Rickets• Other skeletal disorders
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CAUSES of SHORT STATURE
PATHOLOGICAL • Proportionate
– Chromosome defects– Endocrine disorders– Low birth weight short stature (IUGR)– Nutritional deficiency– Chronic systemic disease– Psychosocial deprivation
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Chromosomal Abnormality
• Somatic– Down syndrome
• Sex chromosome– Turner syndrome
• Short stature (< 144cm)
• Gonadal dysgenesis
• Skeletal deformity– Cubitus valgus– Short metacarpals
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Prader-Willi Syndrome
• Obesity - hyperphagia • Moderate mental retardation • Short stature • Hypogonadism • Small hands and feet • Facies with narrow bifrontal diameter, almond
eyes, full cheeks
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Russell-Silver Syndrome
• Intrauterine growth retardation• Postnatal short stature• Small triangular facies• Limb asymmetry
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Endocrine Causes of Short Stature
• Hypopituitarism - GH deficiency (GHD)• Hypothyroidism• Hypercortisolism• Hypogonadism
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PITUITARY DWARFISM
• PRIMARY PITUITARY DISEASE– Pituitary hormone deficiency– Intrasellar tumor– Other destructive processes
(infection, trauma)
Short stature secondary to hypopituitarism is due to lack of stimulation of growth of long bone
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CHARACTERISTICS OF GHD
1. Diminished growth rate2. Delayed bone age 3. GH (<10 μg/L) 4. Growth response to treatment with hGH
EARLY CLUES TO GH DEFICIENCY5. Hypoglycemia6. Micropenis7. Facial midline malformation8. Neonatal injury
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Hypothyroidism
• Hypothyroidism → short stature– Congenital– Acquired
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Congenital Hypothyroidism
History1. Autoimmune thyroid disease in the family2. Intake of anti-thyroid medication in the mother3. Familial congenital hypothyroidism4. Presence of congenital hypothyroidism
associated with deafness and goiter 5. Prolonged jaundice in the neonate6. Poor suck in the neonate7. Poor cry in the neonate8. Constipation in the neonate
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Congenital Hypothyroidism
PE1. Hypothermia2. Mottled, dry, coarse skin3. Jaundice4. Large fontanelle5. Macroglossia6. Hoarse cry7. Distended abdomen8. Umbilical hernia9. Hypotonia10. Goiter
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Hypercortisolism – Cushing syndrome
• Excessive cortisol
• Short and obese
• Causes:– Endogenous: tumor– Exogenous: prolonged
steroid intake
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Abnormal levels of Sex Hormone
Hypogonadism- – both growth and sexual development may be retarded
Turner syndrome– insufficient amounts of the female sex hormone, estrogen– delays in growth and sexual development
• Precocious puberty– Early growth spurt and premature closure of epiphyses– Adult height: Short
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HISTORY
• Birth weight & birth length• Previous height and weight data (growth velocity)• Time of adolescent development• Dietary history• Past Illnesses• School performance
• Family patterns of growth– the heights of parents, grandparents, siblings, and other
close relatives– any history of early or late puberty (growth spurt and
sexual development) in family members
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Physical Examination
• Height• Weight
• Arm span• Upper & lower body segment
• Dysmorphic features• Associated anomalies
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Work-ups
• X-ray for bone age
• Imaging – CT scan / MRI of sella
• Blood tests:– Blood chemistry– Chromosomal analysis– Hormonal stimulation
testsBone age delayed compared to chronological agein GHD and hypothyroidism
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Blood Tests
• Blood tests – BUN, Cr, Ca, P, alk phosphatase, SGPT– TSH, T4– Cortisol– insulin-like growth factor I (IGF-I)– Chromosomal analysis
• Tests for GH Secretion GH Stimulation tests– GH<10 μg/L
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Treatment of Short Stature
• Depends on etiology– Hypothyroidism: levothyroxine – Growth hormone deficiency: GH– Cushing syndrome
• Tumor removal• Adjust dosage of steroid
– Turner syndrome/ Prader Willi syndrome: GH– Achondroplasia: limb lengthening
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Indications of GH Use in Children
• Growth hormone deficiency• Turner syndrome• Small for gestational age (not catching up in
height)• Prader-Willi syndrome• Chronic renal insufficiency • Idiopathic short stature –
– expected to grow shorter than • 5’3” for boys• 4’11” for girls
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PHYSIOLOGIC EFFECTS OF GH
• Short-term administration of GH promotes– Lipolysis
• loss of visceral adipose tissue - the most dramatic metabolic effect of GH
– stimulates protein synthesis– increases lean body mass– stimulates bone turnover– causes insulin antagonism– alters total body water
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Summary• Normal growth
–Growth velocity–Factors affecting growth
• Short stature– “normal” variants– Pathological short stature needs evaluation
• History, PE
– Treatment depends on etiology• GH therapy is approved in some conditions
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Childhood Obesity
Sept,2, 2009
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Learning Outcomes
Obesity• Identify causes of obesity• Acquire skill in history-taking, physical
examination in a child with obesity• Use growth charts and BMI charts• Propose diagnostic work-ups • Provide treatment plan
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Childhood Obesity
1. Definition
2. Epidemiology
3. Physiology
4. Causes
5. Evaluation
6. Treatment
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Definition of Overweight and Obesity
BMI Category Former Terminology
Recommended Terminology
≥95th percentile Overweight or obesity
Obesity
85th - 94th P At risk of overweight
Overweight
5th to 84th P Healthy weight Healthy weight
< 5th percentile Underweight Underweight
Barlow SE and the Expert Committee. Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: Summary report. Pediatrics. 2007;120;S164-S192.
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OK135S057
Growth (Height and Weight ) Charts
Measurements of weight and height. Plot data on the growth charts.
CDC
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Body Mass Index (BMI)
BMI = Weight (kg)
Height (m2)
BMI charts – examples: CDC, WHO
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OK135S060
In children, BMI is age and gender specific
http://www.cdc.gov/nchs/about/major/nhanes/growthcharts/charts.htm
BMI percentile can be used to identify childhood obesity
95th P
85th P
Obesity
Overweight
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WHO BMI Cut-offs
• Overweight: > +1SD (= =BMI 25 kg/m2 at 19 years) • Obesity: > +2SD (= BMI 30 kg/m2 at 19 years) • Thinness: < -2SD• Severe thinness: < -3SD
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Obesity
Overweight
Normal
Thinness
Severe Thinness
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Epidemiology
Prevalence of overweight and obesity • Of the world’s children and
adolescents aged 5 -17 years, about 10% estimated to be overweight
among them, 1/4 obese
(30-40 million) Report of the International Obesity Task Force to the WHO.Obesity Reviews, 2004
Globally, generally there is 2-3 x ↑Lancet 2002; 360:474
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Epidemiology
In the Philippines, 7th National Nutrition Survey (FNRI):
Prevalence of overweight• 2.0% among 0-5 years-old children• 1.6% among 6-10 years-old children• 4.6% among 11-19 year-old adolescents
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Prevalence of overweight and obesity
Among 2022 adolescents (10-19 years) in private and public schools, Metro Manila (2007-2008)
• 13% overweight (BMI 85-94th P)• 8% obesity (BMI ≥95th P)
0%
20%
40%
60%
80%
<5th 5th-84th 85-94th ≥95th
Cua S. 2008
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Study (S Cua, 2008):Adolescents (n=2022; age: 11-18 yr) from 6 high schools (3 private, 3 public)
The prevalence of overweight about 3-fold higher in the private school students
The prevalence of obesity: 5-fold higher in the private school students
BMI distribution by school type
19.3%
71.9%
6.3%2.5%2.6%
66.2%
18.6%
12.5%
Underweight Healthy Overweight Obesity
Public school
Private school
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Prevalence of overweight among students was higher in Private Schools in Metro Mla
• R. Florentino, et al, (2002) – 1208 male and female students, aged 8-10 yr
– the prevalence of overweight (BMI ≥ 95th P) among private school children was almost 4 x higher than those in public school
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Physiology
• Control system of appetite and satiety– Hypothalamus– Negative feedback loop
• Leptin• Glucose• Insulin• Neuropeptides (neuropeptide Y)• Corticotropin releasing hormone• Pro-opiomelanocortin (POMC)• Resistin (animal studies)• Ghrelin
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Physiology
Obesity causes alterations in endocrine physiology. • ↓ serum GH and ↓ IGFBP-1• blunted prolactin response to TRH• ↓ SHBG
• ↑ GHBP• ↑ insulin level or insulin resistance • normal or ↑ IGF-1 and IGFBP-3• slightly ↑ T3• ↑ cortisol secretion rate but normal serum cortisol levels
and urinary free cortisol excretion • ↑ estrogen but ↓ testosterone in boys• ↑ both estrogen and androgen levels in girls
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Causes
Associated with ↑ growth velocity• Simple or exogenous obesity
– Etiology is multifactorial• Interaction of genetics and environment
Endocrine disruptors
– Energy imbalanceEnergy In - Energy Used = Energy Stored
For every 100 calories excess per day, one will put on 10 pounds per year
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Causes
• Caloric intake has increased– Eating unsupervised, lack of family meals– Eating at multiple sites and frequent snacks – Eating out / take out food – Calorically dense food (fried food)– Big portion– Sugar-added beverages
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Causes
• Physical activity has decreased– Schools with less physical education– After school programs– Safety concerns– Convenience activities– Increased sedentary activities: TV, computer,
video games
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Causes
Associated with ↓ growth velocity• Endocrine causes of obesity
– Hypothyroidism– Glucocorticoid excess– GH deficiency– Brain tumors (craniopharyngioma)– Chromosomal defects
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EvaluationHistory • Previous height and weight, including birth
weight and height• Height and weight of parents and siblings• History of diet and physical activity• Psychosocial history• Parental consanguinity• Symptoms of headache, polyuria, menstrual
irregularities in girls, hypotonia and feeding problem during infancy, neonatal hypoglycemia
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Evaluation
Physical examination• Weight • Height• BMI• Waist circumference• Blood pressure
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Evaluation
Physical examination• Dysmorphic features • Acanthosis nigricans• Striae• Plethora• Body hair (hirsutism)• External genitalia
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Work-ups
• FBS, insulin, HbA1c
• Lipid profiles (cholesterol, triglycerides, HDL, LDL)
• Liver function tests (SGPT or ALT, SGPT or AST)
• Sonography – Liver – fatty liver– Ovaries and uterus in girls – PCOS
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Work-ups
• Hormonal assays when indicated– TSH, T4– LH, FSH– Others like testosterone, SHBG, cortisol
• Chromosomal analysis
• CT scan /MRI – Head – craniopharyngioma– Abdomen- adrenal tumor
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Obesity-related complications
Tibia varaPsychosocial problems:
• Depression • Poor self esteem
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DM and Dyslipidemia
• Diabetes mellitus: FBS 126 mg/dl (7mM/L)• Impaired fasting glucose (IFG): >100
mg/dl (5.5 mM/L)
• Dyslipidemia:– Low HDL: Male: <40 mg/dl (1.03 mM/L)
Female: <50 mg/dl (1.29 mM/L)– High LDL: >110 mg/dl (>2.84 mM/L)– High triglycerides: >150 mg/dl (>1.69 mM/L)
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IMPACT OF CHILDHOOD OBESITY IN ADULTHOOD
• Harvard Growth Study: – 2 x ↑ in mortality (all causes) in obese vs
nonobese adolescents as adults
– 2 x ↑ in CAD mortality
– ↑ risk of colon cancer in males
– ↑ risk of arthritis in females
CAD: Coronary artery disease
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Summary of treatment proposals based on the consensus development conference (March 2004) [i]
Definitions Clinical overweight: BMI ≥85th P Clinical obesity: BMI >95th P on national charts Epidemiological or international studies: WHO / IOTF cutoffs
Preventive strategies
Action is required antenatally, in schools, community facilities, marketing, government and regulatory agencies. [i]
Screening Population screening is required to identify overweight children with BMI >85th P
[i] Speiser PW, Rudolf MCJ, Anhalt H, et al. CONSENSUS STATEMENT: Childhood Obesity. J Clin Endocrinol Metab, March 2005, 90(3):1871–1887.
[i] Davis MM, Gance-Cleveland B, Hassink S, Johnson R, Paradis G, Resnicow G. Recommendations for prevention of childhood obesity. Pediatrics. 2007;120(suppl 4):228–252
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Summary of treatment proposals based on the consensus development conference (March 2004) [i]
Assessment Laboratory assessment of children >95th P:
a) Thyroid and liver function tests, fasting glucose, insulin and lipid profile.
b) Children at ↑ risk for the metabolic syndrome require periodic oral glucose tolerance tests from age 10.
c) Screening for other comorbidities: e.g., hypertension, sleep apnea, orthopedic problems, etc.
[i] Speiser PW, Rudolf MCJ, Anhalt H, et al. CONSENSUS STATEMENT: Childhood Obesity. J Clin Endocrinol Metab, March 2005, 90(3):1871–1887.
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Summary of treatment proposals based on the consensus development conference (March 2004) [i]
Treatment Children with BMI ≥85th P should receive regular lifestyle counseling.Children with BMI >95th P require specialist pediatric care.
Service development
Children with comorbidity or severe obesity should receive their care in a multidisciplinary specialist service.
[i] Speiser PW, Rudolf MCJ, Anhalt H, et al. CONSENSUS STATEMENT: Childhood Obesity. J Clin Endocrinol Metab, March 2005, 90(3):1871–1887.
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Recommendations for Weight Management
BMI >95th P BMI>95th P
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Treatment
Weight Management• Diet• Physical Activity• Behavioral modification• Pharmacotherapy
• Multidisciplinary interventions
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Treatment
• Treatment of obesity-related medical conditions– Hypertension– Dyslipidemia
• Treatment of specific disease– Adrenal tumor – excision– Craniopharyngioma – surgery/ radiotherapy
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Childhood Obesity
1. Overweight / obesity
2. Prevalence is rising
3. Genetic and environmental factors
4. Exogenous obesity and endocrine causes
5. Obesity related conditions/ morbidities
6. Treatment and prevention
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Diabetes Mellitusin Children
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Learning Outcomes
Diabetes mellitus• Identify types of DM• Recognize clinical presentation• Propose diagnostic work-ups • Provide treatment plan
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Diabetes Mellitusin the Pediatric Population
• Diagnosis• Types and Pathophysiology• Clinical Presentation • Management
• Acute complication– DKA– Hypoglycemia
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Diabetes Mellitus (DM)
A heterogeneous group of disorders– Insulin production and/or – insulin action
hyperglycemia
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Diagnosis of DM
Diseases of abnormal carbohydrate metabolism
1. FPG 126 mg/dl (7.0 mmol/l)
2. RBS 200 mg/dl (11.1 mmol/l) & symptoms of DM
3. 2-h plasma glucose 200 mg/dl (11.1mmol/l) during an OGTT
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Classification and Pathophysiology
TYPE PATHOPHYSIOLOGYInsulin secretion (IS) / Insulin resistance (IR)
Type 1 Autoimmune destruction of β cells
Type 2 ↑ IR and β cell insufficiency
Monogenic ↓ IS
Secondary(drugs/ dis)
Various: ↓ IS, ↑ IR
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T1DM
β cell specific
autoimmunity
GenesVirusesToxins
Diet
Susceptibility
Autoantigen
DIABETES
Triggering factors
islet-cell (ICA)glutamic acid decarboxylase (anti-GAD)Insulin (IAA)tyrosine phosphatase IA-2
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T1 DM
Local study (Metro Manila, 1998-1999)99 children (1-14 yr)
– 56 girls– 33 boys
• Prevalence: 2.8 cases /100,000
• Incidence: 0.55 – 0.60 cases /100,000
Japan: 2.4 / 100,000
Sy RA, Chan-Cua S, 1999
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Age Distribution of Diabetic Children and Adolescents in PGH, 2010
0
2
4
6
8
10
12
14
<1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Age in year
Per
ce
nt
Male Female
• Pre-school age
• Pubertal age
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9
8
7
6
5
1975 1980 1985 1990 1995
1
2
3
4
5
6
7
8
Year
Typ
e 2
dia
bet
es i
nci
den
ce(p
er 1
00,0
00 p
er y
ear)
Ob
esity (%)
Type 2 diabetes
Obesity
Pediatric T2DM and Obesity in Japan
Kitigawa T et al. Clin Pediatr (Phila) 1998; 37: 111-115
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Bet
a-ce
ll fu
nct
ion
Insu
lin resistan
ce
Insulin resistance andbeta-cell functionNormal
glycaemia
AgePuberty
Glucoseintolerance
Type2 diabetes
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T2DM
Characterized by • Insulin resistance• secretory defect
• Obesity (BMI >95thP for age & gender)
• Family hx: T2DM in a 1st or 2nd degree relative
• High-risk ethnic group (e.g., Aboriginal, African, Hispanic, South-Asian)
• A history of exposure to DM in utero
• Acanthosis nigricans (insulin resistance)
• Polycystic ovarian syndrome (PCOS)
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T1 & T2 DM in children and adolescentsType 1 Type 2
Age of onset Throughout childhood Pubertal
Prominent race All (low in Asians) Asians
Onset Acute, severe Subtle to severe
Islet autoimmunity Present Unusual
Insulin secretion Very low Variable
Insulin sensitivity Normal Decreased
Ketosis, DKA at onset Common, up to 40% Uncommon
Obesity As in population >90%
% of probands with affected 1o relatives
5-10% ~80%
Mode of inheritance Non-Mendelian, gen’ly sporadic
Non-Mendelian, strongly familial
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Monogenic diabetes - MODY
• Autosomal dominant -(+) Family history
• Account for 1–5% of all cases of diabetes
Ledermann HM. Maturity-onset diabetes of the young (MODY) at least ten times more
common in Europe than previously assumed? Diabetologia 1995;38(12):1482.
• 6 causative gene mutations in insulin and glucose regulation and pancreatic beta cell function
Fajans SS, Bell GI, Polonsky KS. Molecular mechanisms and clinical pathophysiology of
maturity-onset diabetes of the young. N Engl J Med 2001;345(13):971-80
Maturity onset diabetes of the young (MODY)
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Monogenic Diabetes - MODY
• MODY 1• MODY 2• MODY 3
• MODY 4• MODY 5• MODY 6
Genetic defects of β-cell function
Gene mutated• Hepatocyte nuclear factor 4 α (HNF-4a)• Glucokinase (GCK) - mild• Hepatic nuclear factor 1 α (HNF-1α)
– early treatment with insulin• Insulin promoter factor-1 (IPF1)• Hepatic transcription factor 1 b (HNF-1b)• Neuro D1
Owen K, Hattersley AT. Maturity-onset diabetes of the young: from clinical description to molecular genetic characterization. Best Pract Res Clin Endocrinol Metab 2001;15(3):309-23
Confirmed diagnosis by genetic testing
Chromosome
20 712
13172
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Monogenic Diabetes - MODY
Resembles T2DM• Relatively mild• May need no insulin • (-) antibodies
Different from T2DM• not obese• not insulin resistant
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Monogenic diabetes - NDM
Transient • Half of NDM• No need of insulin after a few
weeks or months of age• 2 genes (chromosome 6q24)
HYMA1 and ZAC expressed only from paternal copy– A double dose of one or both
genes
Permanent – diverse etiology• Mutation of KCNJ11 gene
Encoding Kir6.2, a β-cell K channel crucial in regulation of insulin
– Response to sulfonylureas (glibenclamide/ glyburide)
• Mutations of EIF2AK3 gene
Neonatal Diabetes Mellitus (NDM): β-cell dysfunction
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NDM - Wolcott-Rallison syndrome (WRS)
• AR• Neonatal onset / < 6 months• Multiple epiphyseal dysplasia• Convulsions
• Retarded development• Short stature• Liver disease • Nephropathy
TD Manna. J Pediatr (Rio J). 2007;83(5 Suppl):S178-183Valerie Senee, et al.Diabetes 53:1876–1883, 2004
Mutations of EIF2AK3 gene – pancreatic eukaryotic initiation factor 2 kinase (2p12)
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Genetic Defects/ Syndromes
Genetic Syndromes• Down syndrome• Klinefelter syndrome• Turner syndrome• Prader-Willi syndrome• Wolfram syndrome
(DIDMOAD)– DI, DM, optic nerve
atrophy, sensorineural deafness
Genetic defects in insulin action
• Type A insulin resistance• Leprechaunism• Rabson-Mendenhall
syndrome• Lipoatrophic diabetes
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Medication-induced DM
• Glucocorticoids- severe hyperglycemia requiring insulin therapy
• Chemo-therapeutic agents (L-asparaginase) and immunosuppressants (cyclosporine and tacrolimus) – direct pancreatic beta cell toxicity– interference with insulin secretion – induction of insulin resistance
• Atypical anti-psychotics and anti-seizure medications
Lindenmayer JP, Nathan AM, Smith RC. Hyperglycemia associated with the use of atypical antipsychotics. J Clin Psychiatry 2001;62 Suppl 23:30-8.
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Endocrine Diosorders
• Acromegaly • Cushing's
syndrome • Glucagonoma • Pheochromocyto
ma
• ↓ glucose uptake/ ↑gluconeogenesis
• ↓ glucose uptake
• ↑ gluconeogenesis/ ↑ glycogenolysis
• ↓ glucose uptake/ ↑ glycogenolysis
Mostly ↑ counter-regulatory hormone effects
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DM Children differ from adults
• Insulin sensitivity related to sexual maturity
• Physical growth
• Ability to provide self-care
• Neurologic vulnerability to hypoglycemia
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Clinical Presentations of DM
• Non-emergency: 3 P’s– Polyuria, polydipsia, polyphagia– Recent onset of enuresis in a previously toilet-trained
child – Weight loss– Fungal infection – Oral / Vaginal candidiasis - in girls– Vomiting – Irritability and decreasing school performance– Recurrent skin infections
• Emergency: DKA
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Diabetic Ketoacidosis (DKA)• ↓ ↓ ↓ insulin levels • ↑ keto acids
• Abdominal discomfort, nausea, and emesis• Dehydration • Weakness • Polyuria
• Kussmaul respirations (deep, heavy, rapid breathing), fruity breath odor (acetone)
• Diminished neurocognitive function• Coma
• About 20–40% of children with new-onset diabetes progress to DKA before diagnosis.
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2006 American Diabetes Association. From Diabetes Care, Vol. 29, 2006; 1150–1159.
↓ insulin↑counter-regulatory hormones
Hyperglycemia
Absolute insulin deficiency
Stress, infection or insufficient insulin intake
↑ Lipolysis ↓Glucose utilization↑Proteolysis
↓Protein synthesis ↑Glycogenolysis
↑Gluconeogenesis
Acidosis
↑Ketogenesis
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Monitoring
Nutrition Exercise Medication
Management of Diabetes Mellitus
Child & Family
Multidisciplinary team of specialists
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Insulin Types and Action Profiles
Rapid- acting
Short-acting
Intermediate –acting (NPH)
Intermediate-acting (Lente)
Long-acting
Premixed (75/25)
Premixed (70/30)
Premixed (50/50)
Make a choice
• Combination
Teach injection
• How
• Where
Dosage
0.5-1 U/ kg / day
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Actions of Oral Hypoglycemic Agents Address Different Defects of Type 2 Diabetes
Oral sulfonylurea Increase insulin secretion
DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med. 1999; 131;281-303Felig P. Bergman M. The endocrine pancreas: diabetes mellitus. In: Felig P. Baxter JD, Frohman LA, eds.Endocrinology and Metabolism. New York NY: McGraw-Hill Inc: 1995:1107-1250.Saltiel AR: Olefsky JM. Thiazolidinediones in the treatment of insulin resistance and type II diabetes. Diabetes. 1996;45:1661-1669.
Class Primary Site of Action Primary Mechanism of Action
Pancreas
LiverBiguanide
Thiazolidinedione
Alpha-glucosidaseinhibitor
Decrease gastrointestinalabsorption of glucose
Reduce basal hepatic glucose production
Enhance insulin-stimulatedGlucose uptake
Intestine
Muscle
Oral Hypoglycemic Agents
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Principles of DM Management
Aims – • To attain good glycemic control• To ensure normal growth (height & weight)• To prevent acute complications• To prevent long-term vascular complications
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Acute Complications
DKA
Diabetes Mellitusin the Pediatric Population
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Islets of Langerhans
b-cell destruction Insulin Deficiency
Adipocytes
Muscle Liver
Decreased Glucose Utilization &Increased Production
Glucagon
IncreasedProtein Catabolism
IncreasedKetogenesisGluconeogenesis,Glycogenolysis
Increased Lipolysis
HyperglycemiaKetoacidosis
HyperTG
PolyuriaVolume Depletion
Ketonuria
StressEpi,Corti
sol
GH
Threshold180 mg/dl
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DKA
DKA
Hyperglycemia (BG >11 mmol/L = 200 mg/dL)
Venous pH <7.3
Bicarbonate <15 mmol/L
Ketonemia and ketonuria
HbA1c
CBC
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DKA
The 3 useful signs for assessing dehydration in young children and predicting acidosis are:
• prolonged capillary refill time (normal capillary refill is 1.5–2 s)
• abnormal skin turgor (tenting or inelastic skin)• abnormal respiratory pattern (hyperpnea)
10% dehydration is suggested by the presence of • weak or impalpable peripheral pulses • hypotension• oliguria
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Management of DKA
• Provide fluid therapy to correct dehydration
• Correct electrolyte imbalance and acidosis
• Give insulin to restore blood glucose to near normal
• Monitor blood glucose
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DKA
Shock ↓ consciousness
Dehydration >5%, acidotic, not in shock
Mild dehydration, Tolerating oral fluid
total body deficit of K
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DKA
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Bicarbonate administration
• Generally, not needed
• Patients with severe acidemia (pH < 6.9) in whom – decreased cardiac contractility and peripheral
vasodilatation can further impair tissue perfusion
• patients with life-threatening hyperkalemia
There is no evidence that bicarbonate is either necessary or safe in DKA.
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• Anion gap = Na - (Cl + HCO3)– normal is 12 ± 2 mmol/L
• In DKA the anion gap is typically 20–30 mmol/L;an anion gap >35 mmol/L suggests concomitant lactic
acidosis
• Na corrected = Na measured +2 x ([glucose - 5.6] / 5.6) mmol/L
• Effective osmolality = 2 x (Na + K) + glucose mOsm/kg
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Warning signs and symptoms of cerebral edema
• Headache & slowing of heart rate• Change in neurological status (restlessness,
irritability, increased drowsiness, incontinence)• Specific neurological signs (e.g., cranial nerve
palsies)• Rising BP• Decreased O2 saturation
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Admit to ICU
• Children with severe DKA – long duration of symptoms– compromised circulation– depressed level of consciousness– those who are at increased risk for cerebral
edema • 5 yr of age• severe acidosis• low PCO2, high BUN
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Hypoglycemia
• Sweating• Trembling• Dizziness• Mood changes• Hunger• Headache• Blurred vision• Extreme tiredness • Pallor
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Management of complications: Hypoglycemia
• Immediate source of glucose – Juice– Milk
• Glucagon
• Dextrose infusion
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Diabetes Mellitusin the Pediatric Population
SUMMARY• Diagnosis• Types and Pathophysiology• Clinical Presentation • Management
• Acute complication– DKA– Hypoglycemia