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Growth (Short Stature, Obesity) Diabetes Mellitus in Children Sioksoan Chan-Cua, MD Associate Professor Pediatric Endocrinologist.

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Presentation on theme: "Growth (Short Stature, Obesity) Diabetes Mellitus in Children Sioksoan Chan-Cua, MD Associate Professor Pediatric Endocrinologist."— Presentation transcript:

1 Growth (Short Stature, Obesity) Diabetes Mellitus in Children Sioksoan Chan-Cua, MD Associate Professor Pediatric Endocrinologist

2 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

3 Growth - Height Normal growth Short stature –Causes Diagnosis –history and physical examination –work-up –treatment / management plan

4 Growth Rate Through Adolescence Girls (11 yr) in Girls (11 yr) cm in Boys (13 yr) cm3 - 5 in Birth to 1 year: cm ( 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 Length: 50 cm (20 in ) Weight: 3 kg (7 lb)

5 DEFINITIONS SHORT STATURE –Height < 3 rd percentile for age GROWTH FAILURE –Growth rate < 5 cm/year after age 2 years Short Stature with Slow Growth Rate

6 Factors Affecting Growth Nutrition (malnutrition) Diseases (chronic diseases) Genes/ heredity Hormones Psychological factors

7 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

8 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 pituitary Ptx 2 is expressed in the somatotrophs (S), lactotrophs (L), thyrotrophs (T) & gonadotrophs Lhx3 (LIM-3/ P-Lim)maintenance function PROP – 1required for S, L, T determination Pit-1 (GHF-1, POU1F1) development of S, L, T cell-specific gene expression and regulation

9 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)

10 Hormonal Control of Growth Pituitary 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

11 Causes of Short Stature

12 Familial Short Stature

13 FAMILIAL SHORT STATURE Growth may be reduced between 6 & 18 months then growth becomes steady but below the 5 th P No weight deficits for height and no bone age delay (BA = CA) TREATMENT: –None –Long term GH results in very modest height increase

14 Constitutional Growth Delay

15 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

16 CAUSES of SHORT STATURE PATHOLOGICAL Disproportionate –Bone development disorders (Skeletal dysplasia) AchondroplasiaAchondroplasia RicketsRickets Other skeletal disordersOther skeletal disorders

17 CAUSES of SHORT STATURE PATHOLOGICAL Proportionate –Chromosome defects –Endocrine disorders –Low birth weight short stature (IUGR) –Nutritional deficiency –Chronic systemic disease –Psychosocial deprivation

18 Chromosomal Abnormality Somatic –Down syndrome Sex chromosome –Turner syndrome Short stature (< 144cm) Gonadal dysgenesis Skeletal deformity –Cubitus valgus –Short metacarpals

19 Prader-Willi Syndrome Obesity - hyperphagia Moderate mental retardation Short stature Hypogonadism Small hands and feet Facies with narrow bifrontal diameter, almond eyes, full cheeks

20 Russell-Silver Syndrome Intrauterine growth retardation Postnatal short stature Small triangular facies Limb asymmetry

21 Endocrine Causes of Short Stature Hypopituitarism - GH deficiency (GHD) Hypothyroidism Hypercortisolism Hypogonadism

22 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

23 CHARACTERISTICS OF GHD 1.Diminished growth rate 2.Delayed bone age 3.GH (<10 μg/L) 4.Growth response to treatment with hGH EARLY CLUES TO GH DEFICIENCY 1.Hypoglycemia 2.Micropenis 3.Facial midline malformation 4.Neonatal injury

24 Hypothyroidism Hypothyroidism → short stature –Congenital –Acquired

25 Congenital Hypothyroidism History 1.Autoimmune thyroid disease in the family 2.Intake of anti-thyroid medication in the mother 3.Familial congenital hypothyroidism 4.Presence of congenital hypothyroidism associated with deafness and goiter 5.Prolonged jaundice in the neonate 6.Poor suck in the neonate 7.Poor cry in the neonate 8.Constipation in the neonate

26 Congenital Hypothyroidism PE 1.Hypothermia 2.Mottled, dry, coarse skin 3.Jaundice 4.Large fontanelle 5.Macroglossia 6.Hoarse cry 7.Distended abdomen 8.Umbilical hernia 9.Hypotonia 10.  Goiter

27 Hypercortisolism – Cushing syndrome Excessive cortisol Short and obese Causes: –Endogenous: tumor –Exogenous: prolonged steroid intake

28 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

29 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

30 Physical Examination Height Weight Arm span Upper & lower body segment Dysmorphic features Associated anomalies

31 Work-ups X-ray for bone age Imaging – CT scan / MRI of sella Blood tests: –Blood chemistry –Chromosomal analysis –Hormonal stimulation tests Bone age delayed compared to chronological age in GHD and hypothyroidism

32 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

33 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

34 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

35 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

36 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

37 Childhood Obesity Sept,2, 2009

38 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

39 Childhood Obesity 1.Definition 2.Epidemiology 3.Physiology 4.Causes 5.Evaluation 6.Treatment

40 Definition of Overweight and Obesity BMI CategoryFormer Terminology Recommended Terminology ≥95 th percentileOverweight or obesity Obesity 85 th - 94 th PAt risk of overweight Overweight 5 th to 84 th PHealthy weight < 5 th percentileUnderweight 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.

41 OK135S057 Growth (Height and Weight ) Charts Measurements of weight and height. Plot data on the growth charts. CDC

42 Body Mass Index (BMI) BMI = Weight (kg) Height (m 2 ) BMI charts – examples: CDC, WHO

43 OK135S060 In children, BMI is age and gender specific BMI percentile can be used to identify childhood obesity 95 th P 85 th P Obesity Overweight

44 WHO BMI Cut-offs Overweight: > +1SD (= =BMI 25 kg/m 2 at 19 years) Obesity: > +2SD (= BMI 30 kg/m 2 at 19 years) Thinness: < -2SD Severe thinness: < -3SD

45 Obesity Overweight Normal Thinness Severe Thinness

46 Epidemiology Prevalence of overweight and obesity Of the world’s children and adolescents aged 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

47 Epidemiology In the Philippines, 7 th 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 year-old adolescents

48 Prevalence of overweight and obesity Among 2022 adolescents (10-19 years) in private and public schools, Metro Manila ( ) 13% overweight (BMI th P) 8% obesity (BMI ≥95 th P) 0% 20% 40% 60% 80% <5th 5th-84th 85-94th≥95th Cua S. 2008

49 Study (S Cua, 2008): Adolescents (n=2022; age: 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

50 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

51 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

52 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

53 Causes Associated with ↑ growth velocity Simple or exogenous obesity –Etiology is multifactorial Interaction of genetics and environment Endocrine disruptors –Energy imbalance Energy In - Energy Used = Energy Stored For every 100 calories excess per day, one will put on 10 pounds per year

54 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

55 Causes Physical activity has decreased –Schools with less physical education –After school programs –Safety concerns –Convenience activities –Increased sedentary activities: TV, computer, video games

56 Causes Associated with ↓ growth velocity Endocrine causes of obesity –Hypothyroidism –Glucocorticoid excess –GH deficiency –Brain tumors (craniopharyngioma) –Chromosomal defects

57 Evaluation History 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

58 Evaluation Physical examination Weight Height BMI Waist circumference Blood pressure

59 Evaluation Physical examination Dysmorphic features Acanthosis nigricans Striae Plethora Body hair (hirsutism) External genitalia

60 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

61 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

62 Obesity-related complications Tibia vara Psychosocial problems: Depression Poor self esteem

63 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)

64 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

65 Summary of treatment proposals based on the consensus development conference (March 2004) [i][i] Definitions Clinical overweight: BMI ≥85 th P Clinical obesity: BMI >95 th 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] [i] ScreeningPopulation screening is required to identify overweight children with BMI >85 th P [i][i] Speiser PW, Rudolf MCJ, Anhalt H, et al. CONSENSUS STATEMENT: Childhood Obesity. J Clin Endocrinol Metab, March 2005, 90(3):1871– [i][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

66 Summary of treatment proposals based on the consensus development conference (March 2004) [i][i] Assessment Laboratory assessment of children >95 th 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][i] Speiser PW, Rudolf MCJ, Anhalt H, et al. CONSENSUS STATEMENT: Childhood Obesity. J Clin Endocrinol Metab, March 2005, 90(3):1871–1887.

67 Summary of treatment proposals based on the consensus development conference (March 2004) [i][i] Treatment Children with BMI ≥85 th P should receive regular lifestyle counseling. Children with BMI >95 th P require specialist pediatric care. Service development Children with comorbidity or severe obesity should receive their care in a multidisciplinary specialist service. [i][i] Speiser PW, Rudolf MCJ, Anhalt H, et al. CONSENSUS STATEMENT: Childhood Obesity. J Clin Endocrinol Metab, March 2005, 90(3):1871–1887.

68

69 Treatment Weight Management Diet Physical Activity Behavioral modification Pharmacotherapy Multidisciplinary interventions

70 Treatment Treatment of obesity-related medical conditions –Hypertension –Dyslipidemia Treatment of specific disease –Adrenal tumor – excision –Craniopharyngioma – surgery/ radiotherapy

71 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

72 Diabetes Mellitus in Children

73 Learning Outcomes Diabetes mellitus Identify types of DM Recognize clinical presentation Propose diagnostic work-ups Provide treatment plan

74 Diabetes Mellitus in the Pediatric Population Diagnosis Types and Pathophysiology Clinical Presentation Management Acute complication –DKA –Hypoglycemia

75 Diabetes Mellitus (DM) A heterogeneous group of disorders –Insulin production and/or –insulin action  hyperglycemia

76 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

77 Classification and Pathophysiology TYPEPATHOPHYSIOLOGY Insulin secretion (IS) / Insulin resistance (IR) Type 1Autoimmune destruction of β cells Type 2 ↑ IR and β cell insufficiency Monogenic↓ IS Secondary (drugs/ dis) Various: ↓ IS, ↑ IR

78 T1DM β cell specific autoimmunity Genes Viruses Toxins Diet Susceptibility Autoantigen DIABETES Triggering factors islet-cell (ICA) glutamic acid decarboxylase (anti-GAD) Insulin (IAA) tyrosine phosphatase IA-2

79 T1 DM Local study (Metro Manila, ) 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

80 Age Distribution of Diabetic Children and Adolescents in PGH, 2010 Pre-school age Pubertal age

81 Year Type 2 diabetes incidence (per 100,000 per year) Obesity (%) Type 2 diabetes Obesity Pediatric T2DM and Obesity in Japan Kitigawa T et al. Clin Pediatr (Phila) 1998; 37:

82 Beta-cell function Insulin resistance Insulin resistance and beta-cell function Normal glycaemia Age Puberty Glucose intolerance Type 2 diabetes

83 T2DM Characterized by Insulin resistance secretory defect Obesity (BMI >95 th P 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)

84 T1 & T2 DM in children and adolescents Type 1Type 2 Age of onsetThroughout childhoodPubertal Prominent raceAll (low in Asians)Asians OnsetAcute, severeSubtle to severe Islet autoimmunityPresentUnusual Insulin secretionVery lowVariable Insulin sensitivityNormalDecreased Ketosis, DKA at onsetCommon, up to 40%Uncommon ObesityAs in population>90% % of probands with affected 1 o relatives 5-10%~80% Mode of inheritanceNon-Mendelian, gen’ly sporadic Non-Mendelian, strongly familial

85 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): 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): Maturity onset diabetes of the young (MODY)

86 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): Confirmed diagnosis by genetic testing Chromosome

87 Monogenic Diabetes - MODY Resembles T2DM Relatively mild May need no insulin (-) antibodies Different from T2DM not obese not insulin resistant

88 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

89 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):S Valerie Senee, et al.Diabetes 53:1876–1883, 2004 Mutations of EIF2AK3 gene – pancreatic e ukaryotic i nitiation f actor 2 k inase (2p12)

90 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

91 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.

92 Endocrine Diosorders Acromegaly Cushing's syndrome Glucagonoma Pheochromocytoma ↓ glucose uptake/ ↑gluconeogenesis ↓ glucose uptake ↑ gluconeogenesis/ ↑ glycogenolysis ↓ glucose uptake/ ↑ glycogenolysis Mostly ↑ counter-regulatory hormone effects

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94 DM Children differ from adults Insulin sensitivity related to sexual maturity Physical growth Ability to provide self-care Neurologic vulnerability to hypoglycemia

95 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

96 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.

97 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

98 Monitoring NutritionExercise Medication Management of Diabetes Mellitus Child & Family Multidisciplinary team of specialists

99 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 U/ kg / day

100 Actions of Oral Hypoglycemic Agents Address Different Defects of Type 2 Diabetes Oral sulfonylureaIncrease insulin secretion DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med. 1999; 131; Felig 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: Saltiel AR: Olefsky JM. Thiazolidinediones in the treatment of insulin resistance and type II diabetes. Diabetes. 1996;45: ClassPrimary Site of ActionPrimary Mechanism of Action Pancreas Liver Biguanide Thiazolidinedione Alpha-glucosidase inhibitor Decrease gastrointestinal absorption of glucose Reduce basal hepatic glucose production Enhance insulin-stimulated Glucose uptake Intestine Muscle Oral Hypoglycemic Agents

101 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

102 Acute Complications DKA Diabetes Mellitus in the Pediatric Population

103 Islets of Langerhans  -cell destruction Insulin Deficiency Adipocytes Muscle Liver Decreased Glucose Utilization & Increased Production Glucagon Increased Protein Catabolism Increased Ketogenesis Gluconeogenesis, Glycogenolysis Increased Lipolysis Hyperglycemia Ketoacidosis HyperTG Polyuria Volume Depletion Ketonuria Stress Epi,Cortisol GH Threshold 180 mg/dl

104 DKA Hyperglycemia (BG >11 mmol/L = 200 mg/dL) Venous pH <7.3 Bicarbonate <15 mmol/L Ketonemia and ketonuria HbA1c CBC

105 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

106 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

107 DKA Shock ↓ consciousness Dehydration >5%, acidotic, not in shock Mild dehydration, Tolerating oral fluid total body deficit of K

108 DKA

109 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.

110 Anion gap = Na - (Cl + HCO 3 ) –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

111 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 O 2 saturation

112 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 PCO 2, high BUN

113 Hypoglycemia Sweating Trembling Dizziness Mood changes Hunger Headache Blurred vision Extreme tiredness Pallor

114 Management of complications: Hypoglycemia Immediate source of glucose –Juice –Milk Glucagon Dextrose infusion

115 Diabetes Mellitus in the Pediatric Population SUMMARY Diagnosis Types and Pathophysiology Clinical Presentation Management Acute complication –DKA –Hypoglycemia


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