DIABETES DIABETES Paediatrics and Paediatrics and

AdolesenceAdolesence

Dr Aisling MyersDr Aisling Myers

Clinical LecturerClinical Lecturer

ClassificationClassification Type 1 (Autoimmune, Idiopathic)Type 1 (Autoimmune, Idiopathic) Type 2 Type 2

OthersOthers Genetic defects of Genetic defects of ββ-cell function (e.g. MODY)-cell function (e.g. MODY) Pancreatic diseases (e.g. cystic fibrosis)Pancreatic diseases (e.g. cystic fibrosis) Endocrinopathies (e.g. Cushing Syndrome)Endocrinopathies (e.g. Cushing Syndrome) Iatrogenic (e.g. Glucocorticoids)Iatrogenic (e.g. Glucocorticoids) Infections (e.g. Congenital Rubella)Infections (e.g. Congenital Rubella) Other syndromes (e.g Prader Willi Syndrome)Other syndromes (e.g Prader Willi Syndrome)

Gestational Gestational

Diabetes – Type 1 Diabetes – Type 1

Most common metabolic disease in the Most common metabolic disease in the youngyoung

Third most common chronic disorder in Third most common chronic disorder in childhood after asthma and cerebral palsychildhood after asthma and cerebral palsy

Life threatening, life longLife threatening, life long Incidence rising, presenting at younger Incidence rising, presenting at younger

ageageChronic hyperglycaemiaChronic hyperglycaemiaDefect in insulin secretion / actionDefect in insulin secretion / action

NormoglycaemiaNormoglycaemia

Uncontrolled Diabetes MellitusUncontrolled Diabetes Mellitus

Insulin deficiencyInsulin deficiency

PathogenesisPathogenesis Deficiency of insulin secretionDeficiency of insulin secretion

Prone to ketoacidosisProne to ketoacidosis

T-cell mediated pancreatic islet T-cell mediated pancreatic islet ββ-cell destruction-cell destruction ββ-cell destruction – occurs at variable rate-cell destruction – occurs at variable rate Process begins months/years before presentation with Process begins months/years before presentation with

clinical symptoms. ? Viral triggerclinical symptoms. ? Viral trigger Clinically symptomatic when ~ 90% of Clinically symptomatic when ~ 90% of ββ-cells destroyed-cells destroyed

HLA genes – 8-10 fold risk if HLA-DR3 or HLA-DR4HLA genes – 8-10 fold risk if HLA-DR3 or HLA-DR4

Serological Markers Serological Markers

Serological markers present in 85-90% at Serological markers present in 85-90% at presentationpresentation

Autoimmune pathologic processAutoimmune pathologic process Islet cell Autoantibodies (ICA)Islet cell Autoantibodies (ICA) Insulin Autoantibodies (IAA)Insulin Autoantibodies (IAA)Glutamic Acid Decarboxylase (GAD)Glutamic Acid Decarboxylase (GAD)

EpidemiologyEpidemiology

Over 50% diagnosed before 15 yrsOver 50% diagnosed before 15 yrs T1DM – accounts for >90% of childhood and T1DM – accounts for >90% of childhood and

adolescent diabetesadolescent diabetes Type 2 – becoming more commonType 2 – becoming more common Incidence variable - Highest in Finland.Incidence variable - Highest in Finland. 12 – 15% will have affected first degree relative12 – 15% will have affected first degree relative 3 times more likely to develop diabetes if father 3 times more likely to develop diabetes if father

also affected vs motheralso affected vs mother Screening unethical unless part of trial – no Screening unethical unless part of trial – no

effective methods of preventioneffective methods of prevention

Diagnosis 1Diagnosis 1 Symptoms……plusSymptoms……plus

Hyperglycaemia (random blood sugar Hyperglycaemia (random blood sugar >11mmol/litre)>11mmol/litre)

OrOr Fasting blood sugar >7.0 mmol/litreFasting blood sugar >7.0 mmol/litre

OrOr 2hr post prandial sugar >11 mmol/litre2hr post prandial sugar >11 mmol/litre

OrOr OGTTOGTT

Diagnosis 2Diagnosis 2

PresentationPresentation Polyuria, polydipsia, weight lossPolyuria, polydipsia, weight loss Glycosuria, KetonuriaGlycosuria, Ketonuria Diabetic Ketoacidosis (DKA) – urgentDiabetic Ketoacidosis (DKA) – urgent Non-ketotic hyperosmolar stateNon-ketotic hyperosmolar state Recent onset enuresis in previously trained childRecent onset enuresis in previously trained child Vaginal candidiasis (prepubertal)Vaginal candidiasis (prepubertal) VomitingVomiting Chronic weight loss, failure to thriveChronic weight loss, failure to thrive Recurrent skin infectionsRecurrent skin infections

ManagementManagement

Urgent (same day) referral to multidisciplinary Urgent (same day) referral to multidisciplinary paediatric diabetes care teampaediatric diabetes care team

AdmissionAdmission or home based care or home based care Admit:Admit:

DKADKA <2 yrs old<2 yrs old Social / Emotional issuesSocial / Emotional issues Family living long distance from hospitalFamily living long distance from hospital Peripheral hospitalPeripheral hospital

DKADKA

Clinical historyClinical history Polyuria, polydipsia, wgt loss, abdo pain, weakness, Polyuria, polydipsia, wgt loss, abdo pain, weakness,

vomiting, confusion, stupor, coma.vomiting, confusion, stupor, coma.

Clinical signsClinical signs Dehydration, smell of ketones, lethargy, drowsiness, Dehydration, smell of ketones, lethargy, drowsiness,

Kussmaul breathingKussmaul breathing

Biochemical signsBiochemical signs Ketones (blood/urine), hyperglycaemia (>11), acidosis Ketones (blood/urine), hyperglycaemia (>11), acidosis

(pH < 7.3), other electrolyte abnormalities(pH < 7.3), other electrolyte abnormalities

DKADKA

AAirway irway BBreathing reathing CCirculation (ABC)irculation (ABC) Admit ICUAdmit ICU IV access x 2IV access x 2 OxygenOxygen Fluid resuscitation / IV Insulin / PotassiumFluid resuscitation / IV Insulin / Potassium Electrolyte monitoring (hrly, 2hrly, 4hrly) – KElectrolyte monitoring (hrly, 2hrly, 4hrly) – K+ +

Close monitoring Close monitoring Sepsis/InfectionSepsis/Infection Neurological deterioration Neurological deterioration Cerebral oedemaCerebral oedema

InsulinInsulin

Subcutaneous insulin Subcutaneous insulin when clinically well when clinically well and tolerating food / and tolerating food / fluidsfluids

Injection sitesInjection sites AbdomenAbdomen ThighsThighs ButtocksButtocks

Insulin PreparationsInsulin Preparations

PreparationPreparation OnsetOnset DurationDuration

Rapid acting*Rapid acting* 15 mins15 mins 2 – 5 hours2 – 5 hours

Short actingShort acting 30 – 60 mins30 – 60 mins Up to 8 hoursUp to 8 hours

Intermediate Intermediate actingacting

1 – 2 hours1 – 2 hours 16 – 35 hours16 – 35 hours

Long actingLong acting 1 – 2 hours1 – 2 hours > 24 hours> 24 hours

Insulin RegimensInsulin Regimens

1, 2 or 3 injections per day: rapid or short 1, 2 or 3 injections per day: rapid or short acting insulin premixed or self mixed with acting insulin premixed or self mixed with intermediate acting insulinintermediate acting insulin

MDI regimen: rapid or short acting insulin MDI regimen: rapid or short acting insulin before meals with intermediate or long before meals with intermediate or long acting insulinacting insulin

Insulin pump therapy (CSII) – most Insulin pump therapy (CSII) – most physiological. Requires commitment , physiological. Requires commitment , competence and good family supportcompetence and good family support

Phases of DiabetesPhases of Diabetes Preclinical diabetesPreclinical diabetes

Months or years prior to presentationMonths or years prior to presentation Antibodies (Islet cell, Insulin, Glutamic Acid Antibodies (Islet cell, Insulin, Glutamic Acid

Decarboxylase) - positiveDecarboxylase) - positive PresentationPresentation Partial remissionPartial remission (“ (“HoneymoonHoneymoon” Phase)” Phase)

80% of cases transient decrease in insulin 80% of cases transient decrease in insulin requirementsrequirements

Duration – weeks to monthsDuration – weeks to months Important to inform parents that this phase is transient Important to inform parents that this phase is transient

ChronicChronic Lifelong insulin therapyLifelong insulin therapy

EducationEducation

InsulinInsulinMonitoring glycaemic control (HbA1C)Monitoring glycaemic control (HbA1C)DietDietExerciseExerciseSmoking / Alcohol / Substance misuseSmoking / Alcohol / Substance misuse Intercurrent illness (sick days)Intercurrent illness (sick days)Hypoglycaemic episodesHypoglycaemic episodes

Avoidance, detection, managementAvoidance, detection, management

Multidisciplinary TeamMultidisciplinary Team

Consultant and diabetic teamConsultant and diabetic teamDiabetic Nurse SpecialistsDiabetic Nurse SpecialistsDieticianDieticianPsychologyPsychologySocial WorkerSocial WorkerOphthalmology Ophthalmology ChiropodyChiropodyGPGP

Follow-UpFollow-Up

Aim for frequent blood sugar monitoring Aim for frequent blood sugar monitoring (usually 4 BM’s daily – fingerprick)(usually 4 BM’s daily – fingerprick)

Aim for pre-prandial sugar: 4 – 8 mmol/LAim for pre-prandial sugar: 4 – 8 mmol/LAim for post-prandial sugar: < 10mmol/LAim for post-prandial sugar: < 10mmol/LAdjust insulin doses accordinglyAdjust insulin doses accordinglyLiaise with diabetic team (phone / clinic)Liaise with diabetic team (phone / clinic)Monitor sugars more often during Monitor sugars more often during

intercurrent illnessintercurrent illness

Clinic VisitsClinic Visits Monitor growth (height, weight, BMI)Monitor growth (height, weight, BMI) Pubertal development Pubertal development HbA1C (< 7.5%)HbA1C (< 7.5%) Check injection sitesCheck injection sites Review foot careReview foot care Annual screenAnnual screen

RetinopathyRetinopathy Nephropathy (Microalbuminuria, Blood Pressure)Nephropathy (Microalbuminuria, Blood Pressure) Associated conditionsAssociated conditions

Thyroid diseaseThyroid disease Coeliac DiseaseCoeliac Disease

Ongoing CareOngoing Care

Constant re-educationConstant re-educationEncourage family involvementEncourage family involvementPsychology (NB in teenage years)Psychology (NB in teenage years)Tailor insulin therapy and delivery Tailor insulin therapy and delivery

methods to each patient / familymethods to each patient / familyScreen for complicationsScreen for complicationsTransition to adult care – smoothTransition to adult care – smooth

Surgical ProceduresSurgical Procedures

In centres with facilities for care of In centres with facilities for care of children/young people with diabeteschildren/young people with diabetes

Agree protocol for safe management.Agree protocol for safe management.Ensure first on list.Ensure first on list. Inform anaesthetic teamInform anaesthetic teamCheck regular blood sugarsCheck regular blood sugarsCheck electrolytes (K)Check electrolytes (K)Check for glycosuria, ketonuriaCheck for glycosuria, ketonuria

ComplicationsComplications Short Term / OngoingShort Term / Ongoing

HypoglycaemiaHypoglycaemia DKADKA Sick daysSick days Lipohypertrophy (48%)Lipohypertrophy (48%) PsychologicalPsychological

Long TermLong Term RetinopathyRetinopathy NephropathyNephropathy NeuropathyNeuropathy Macrovascular DiseaseMacrovascular Disease

HypoglycaemiaHypoglycaemia

Carry T1DM identification (bracelet)Carry T1DM identification (bracelet) Rapid access to CHO and blood sugar monitorRapid access to CHO and blood sugar monitor Educate carers re glucagon administration and Educate carers re glucagon administration and

advice to seek medical assistance if failing to advice to seek medical assistance if failing to respond (seizures can occur if untreated)respond (seizures can occur if untreated)

Patients – increase awareness and respond Patients – increase awareness and respond appropriatelyappropriately

Avoid over corrections at meals especially at Avoid over corrections at meals especially at night – overnight or fasting hyponight – overnight or fasting hypo

Avoid very low HbA1CAvoid very low HbA1C

DKADKA

Untreated – stupor, coma, deathUntreated – stupor, coma, deathFollow proposed guidelines for institutionFollow proposed guidelines for institution Initial management in HDUInitial management in HDUTransfer to paeds ICU if not respondingTransfer to paeds ICU if not respondingOutrule co-existing sepsisOutrule co-existing sepsisMonitor closely for signs of deteriorationMonitor closely for signs of deterioration

Impaired consciousnessImpaired consciousnessSuspected cerebral oedemaSuspected cerebral oedema

Sick DaysSick Days

Sick Day RulesSick Day RulesExtra blood sugarsExtra blood sugarsCheck for ketonesCheck for ketonesHrly / 2 hrly snacksHrly / 2 hrly snacks If persistent vomiting or if not tolerating – If persistent vomiting or if not tolerating –

bring to hospitalbring to hospitalRegular phone contact with nurse Regular phone contact with nurse

specialist/teamspecialist/teamNEVER OMIT INSULINNEVER OMIT INSULIN

Psychological / Social IssuesPsychological / Social Issues

Emotional / BehaviouralEmotional / BehaviouralFamily ConflictFamily ConflictAnxiety / DepressionAnxiety / DepressionEating DisordersEating DisordersCognitive DisordersCognitive DisordersBehavioural / Conduct DisordersBehavioural / Conduct DisordersNon – compliance Non – compliance

ComplicationsComplications

Long Term - RetinopathyLong Term - Retinopathy

Visual impairmentVisual impairment BlindnessBlindness Poor glycaemic Poor glycaemic

controlcontrol Laser treatment if Laser treatment if

sight threateningsight threatening Ophthalmology check Ophthalmology check

annually from 12 annually from 12 years or if diagnosed years or if diagnosed >5yrs>5yrs

Long Term - NephropathyLong Term - Nephropathy

Renal failureRenal failure HypertensionHypertension Early morning urine for Early morning urine for

microalbuminuriamicroalbuminuria Albumin:Creatinine ratioAlbumin:Creatinine ratio Monitor BP at clinic visitsMonitor BP at clinic visits Screen annually from 12 Screen annually from 12

yrs or if diagnosed > 5yrsyrs or if diagnosed > 5yrs

Long Term - MacrovascularLong Term - Macrovascular

StrokeStroke

Ischaemic Heart Ischaemic Heart DiseaseDisease

Peripheral Vascular Peripheral Vascular DiseaseDisease

Associated Associated Conditions/ComplicationsConditions/Complications

Impaired growth and developmentImpaired growth and developmentLate pubertal developmentLate pubertal developmentObesity (excessive exogenous insulin Obesity (excessive exogenous insulin

assoc with high energy intake)assoc with high energy intake)Autoimmune conditionsAutoimmune conditions

HypothyroidismHypothyroidismHyperthyroidismHyperthyroidismCoeliac DiseaseCoeliac DiseaseAddison’s DiseaseAddison’s Disease

Other types of DiabetesOther types of Diabetes

Type 2 DiabetesType 2 Diabetes

Rising prevalence – associated with Rising prevalence – associated with increasing obesityincreasing obesity

Type 2 DiabetesType 2 Diabetes

Insulin resistanceInsulin resistanceAcanthosis nigricansAcanthosis nigricansHigh insulin or c-peptide levelsHigh insulin or c-peptide levelsDyslipidemiaDyslipidemiaPolycystic ovarian syndromePolycystic ovarian syndrome

More common in ethnic minority groupsMore common in ethnic minority groupsJapan – more common than T1DMJapan – more common than T1DM

Type 2 DiabetesType 2 Diabetes

Commonly presents in mid-pubertyCommonly presents in mid-pubertyConfused with MODY (monogenic maturity Confused with MODY (monogenic maturity

onset diabetes of the young)onset diabetes of the young)Screen if obese, positive family history or Screen if obese, positive family history or

signs of insulin resistancesigns of insulin resistanceLifestyle changes – diet, exerciseLifestyle changes – diet, exercisePharmacotherapy – not licensed in Pharmacotherapy – not licensed in

childrenchildrenEarly intervention – best preventionEarly intervention – best prevention

Neonatal DiabetesNeonatal Diabetes

Very rare (1 in 400,000 births)Very rare (1 in 400,000 births) Insulin requiring hyperglycaemia in first 3-6 mths Insulin requiring hyperglycaemia in first 3-6 mths

of lifeof life May be associated with IUGR (intra uterine May be associated with IUGR (intra uterine

growth retardation)growth retardation) 50% cases transient50% cases transient Permanent – associated with pancreatic aplasia, Permanent – associated with pancreatic aplasia,

genetic mutationsgenetic mutations Predisposition to impaired glucose tolerance and Predisposition to impaired glucose tolerance and

Type 2 diabetes in later lifeType 2 diabetes in later life

Cystic Fibrosis (CFRD)Cystic Fibrosis (CFRD) Insulin deficiencyInsulin deficiency Insulin resistanceInsulin resistance

InfectionsInfections Medications (steroids, bronchodilators)Medications (steroids, bronchodilators)

Occurs late in disease (adolescence, early adulthood)Occurs late in disease (adolescence, early adulthood) Cirrhosis contributes to insulin resistanceCirrhosis contributes to insulin resistance Onset of CFRD – poor prognostic indicatorOnset of CFRD – poor prognostic indicator Poor control – promotes catabolismPoor control – promotes catabolism Screening – OGTT as part of annual screen >10yrsScreening – OGTT as part of annual screen >10yrs Insulin doses usually smaller than in classic T1DM Insulin doses usually smaller than in classic T1DM

MODYMODY

Maturity Onset Diabetes of the YoungMaturity Onset Diabetes of the YoungSingle gene disorder causing Single gene disorder causing ββ cell cell

dysfunctiondysfunctionAutosomal dominant family historyAutosomal dominant family historyEndogenous insulin secretionEndogenous insulin secretionNot prone to ketoacidosisNot prone to ketoacidosisNo signs of insulin resistanceNo signs of insulin resistanceUsually require less insulin than classic T1DMUsually require less insulin than classic T1DMMutations found in >80% of patients (5)Mutations found in >80% of patients (5)

Other causesOther causes

Drug-induced diabetesDrug-induced diabetesNeurosurgery (Dexamethasone)Neurosurgery (Dexamethasone)Oncology (chemotherapy)Oncology (chemotherapy)

Stress HyperglycaemiaStress HyperglycaemiaReported in up to 5% attendances to A&EReported in up to 5% attendances to A&EAcute illness, trauma, post seizure, feverAcute illness, trauma, post seizure, feverRecheck blood sugar series when wellRecheck blood sugar series when well

Islet Cell TransplantationIslet Cell Transplantation

Islet cells replaced with harvested donor Islet cells replaced with harvested donor cellscells

Typically receive cells from up to 3 donorsTypically receive cells from up to 3 donorsExperimental therapyExperimental therapyShortage of donor materialShortage of donor materialStill require insulin therapyStill require insulin therapyAnti-rejection drugs – severe side effectsAnti-rejection drugs – severe side effects

The FutureThe Future

Key PointsKey Points

Lifelong diseaseLifelong diseaseNever omit insulinNever omit insulinHealthy lifestyle for all the familyHealthy lifestyle for all the familyGood glycaemic controlGood glycaemic controlScreen for complicationsScreen for complications

Prevention better than cure!Prevention better than cure!

Thank YouThank You