DEFINITION a metabolic disorder of multiple etiologies characterized by chronic

hyperglycemia with disturbances

of carbohydrate, fat and protein metabolism resulting from defects

of insulin secretion, insulin action or both.

DIABETES EPIDEMIOLOGYDiabetes is the most common

endocrine problem worldwide.Incidence of diabetes is alarmingly

increasing all over the globe.Incidence of childhood diabetes

range between 3-50/100,000 worldwide

WHO CLASSIFICATION 2000Is based on etiology not on type of

treatment or age of the patient.Type 1 Diabetes

(idiopathic or autoimmune -cell destruction)

Type 2 Diabetes (defects in insulin secretion or action)

Other specific types

WHO CLASSIFICATION/2

Both type 1 & type 2 can be further subdivided into:Not insulin requiringInsulin requiring for controlInsulin requiring for survival

Gestational diabetes is a separate entity

Impaired Glucose Tolerance (IGT) indicates blood glucose levels between normal & diabetic cut off points during glucose tolerance test.

DIAGNOSTIC CRITERIAFasting blood glucose

levelDiabetic

Plasma >7.0 mmolCapillary >6.0 mmol

IGT Plasma 6.0-6.9 mmolCapillary 5.6-6.0 mmol

1 mg/dl = 0.05556 mmol/l

2 hours after glucose load

(Plasma or capillary BS)

IGT7.8-11.0

Diabetic level> 11.1 (200 mg)

Types of Diabetes in ChildrenType 1 diabetes mellitus accounts

for >90% of cases.Type 2 diabetes is increasingly

recognized in children with presentation like in adults.

Permanent neonatal diabetesTransient neonatal diabetesMaturity-onset diabetes of the

youngSecondary diabetes e.g. in cystic

fibrosis or Cushing syndrome.

MODY(Maturity onset diabetes of the young )

Usually affects older children & adolescentsNot rare as previously considered5 subclasses are identified, one subclass has

specific mode of inheritance (AD) Not associated with immunologic or genetic

markersInsulin resistance is present

TRANSIENT NEONATAL DIABETESObserved in both term & preterm

babies, but more common in preterm Caused by immaturity of islet -cellsPolyuria & dehydration are

prominent, but baby looks well & suck vigorously

Highly sensitive to insulinDisappears in 4-6 weeks

PERMANENT NEONATAL DIABETES A familial form of diabetes that

appear shortly after birth & continue for life

The usual genetic & immunologic markers of Type 1 diabetes are absent

Insulin requiring, but ketosis resistant

Is often associated with other congenital anomalies & syndromes e.g. Wolcott-Rallison syndrome.

TYPE 1 DIABETES: ETIOLOGYType 1 diabetes mellitus is an

autoimmune disease. It is triggered by environmental

factors in genetically susceptible individuals.

Both humoral & cell-mediated immunity are stimulated.

GENETIC FACTORSEvidence of genetics is shown in Ethnic differencesFamilial clusteringHigh concordance rate in twinsSpecific genetic markersHigher incidence with genetic

syndromes or chromosomal defects

AUTOIMMUNITYCirculating antibodies against -

cells and insulin.Immunofluorescent antibodies &

lymphocyte infiltration around pancreatic islet cells.

Evidence of immune system activation. Circulating immune complexes with high IgA & low interferon levels.

Association with other autoimmune diseases.

ENVIRONMENTAL INFLUENCESeasonal & geographical variation.Migrants take on risk of new home.Evidence for rapid temporal changes.Suspicion of environmental agents

causing disease which is confirmed by case-control experimental animal studies.

ENVIRONMENTALViruses

Coxasckie BMumpsRubellaReoviruses

Nutrition & dietary factorsCow’s milk proteinContaminated sea food

OTHER MODIFYING FACTORSThe counter-regulatory hormones:

glucagoncortisol,catecholaminesthyroxin,GH & somatostatinsex hormones

Emotional stress

ETIOLOGIC MODELThe etiologic model of type 1

diabetes resembles that of Rheumatic fever.

Rheumatic fever was prevented by elimination of the triggering environ. factor (-streptococci).

Similarly type 1 diabetes may be prevented by controlling the triggering factors in high risk persons.

CLINICAL PRESENTATIONSClassical symptom triad:

polyuria, polydipsia and weight loss

DKAAccidental diagnosisAnorexia nervosa like illness

DIAGNOSISIn symptomatic children a random

plasma glucose >11 mmol (200 mg) is diagnostic.

A modified OGTT = oral glucose tolerance test (fasting & 2h) may be needed in asymptomatic children with hyperglycemia if the cause is not obvious.

Remember: acute infections in young non-diabetic children can cause hyperglycemia without ketoacidosis.

Children ingest 1.75 g/kg body weight in a similar volume of water by ratio (max 75 g as for adults).

Glycated haemoglobin

Although HbA1c testing is mainly used for monitoring blood sugar control in patients with diabetes, the WHO now recommends that HbA1c can be used as a diagnostic test for diabetes, provided that stringent quality assurance tests are in place and assays are standardised to criteria aligned to the international reference values. An HbA1c of 6.5% is recommended as the cut-off point for diagnosing diabetes. A value less than 6.5% does not exclude diabetes diagnosed using glucose tests.

NATURAL HISTORYDiagnosis & initiation of insulin

Period of metabolic recovery

Honeymoon phase

State of total insulin dependency

METABOLIC RECOVERYDuring metabolic recovery the patient mayDevelop one or more of the following:

Hepatomegaly Peripheral edema Loss of hair Problem with visual acuity

These are caused by deposition of glycogen & metabolic re-balance.

HONEYMOON PERIODDue to -cell reserve optimal function

& initiation of insulin therapy.Leads to normal blood glucose level

without exogenous insulin.Observed in 50-60% of newly diagnosed

patients & it can last up to one year but it always ends.

Can confuse patients & parents if not educated about it early.

COMPLICATIONS OF DIABETES ARE NUTRITIONAL, METABOLIC AND CHRONIC

DEGENERATIVEAcute:

DKA (Diabetic ketoacidosis )Hypoglycemia

Late-onset:

Retinopathy NeuropathyNephropathyIschemic heart disease & stroke

TREATMENT GOALSPrevent death

Achieve biochemical control

Maintain growth and development

Prevent acute complications

Prevent or delay late-onset

complications

TREATMENT ELEMENTS

1. Insulin therapy2. Diet and meal planning3. Exercise Education Monitoring

HbA1c every 2-monthsHome regular BG monitoring Home urine ketones tests when

indicated

EDUCATIONEducate child & care givers about:

Diabetes Insulin Life-saving skills Recognition of Hypo & DKA Meal plan Sick-day management

INSULINA polypeptide made of 2 -chains.

Discovered by Bants & Best in 1921.

Animal types (porcine & bovine) were used before the introduction of human-like insulin (DNA-recombinant types).

Recently more potent insulin analogs are produced by changing aminoacid sequence.

FUNCTION OF INSULIN Insulin being an anabolic hormone

stimulates protein & fatty acids synthesis.

Insulin decreases blood sugar 1. By inhibiting hepatic glycogenolysis and

gluconeogenesis.2. By stimulating glucose uptake,

utilization & storage by the liver, muscles & adipose tissue.

TYPES OF INSULIN Short acting (neutral, soluble, regular)Short acting (neutral, soluble, regular)

Peak 2-3 hours & duration up to 8 hoursIntermediate actingIntermediate acting

Isophane (peak 6-8 h & duration 16-24 h)Biphasic (peak 4-6 h & duration 12-20 h)Semilente (peak 5-7 h & duration 12-18 h)

Long acting (lente, ultralente & PZI)Long acting (lente, ultralente & PZI)Peak 8-14 h & duration 20-36 h

INSULIN CONCENTRATIONS

Insulin is available in different

concentrations 40, 80 & 100 Unit/ml.

WHO now recommends U 100 to be

the only used insulin to prevent

confusion.

Special preparation for infusion

pumps is soluble insulin 500 U/ml.

INSULIN REGIMENSTwice daily: either NPH alone or NPH+SI.Thrice daily: SI before each meal and NPH

only before dinner.Intensive 4 times/day: SI before meals +

NPH or Glargine at bed time.Continuous s/c infusion using pumps

loaded with SI.

NPH insulin (or neutral protamine Hagedorn) (also known as Humulin N, Novolin N, is an intermediate-acting insulin

Insulin glargine, Lantus, is a long-acting basal insulin analogue that slowly release insulin, giving a long duration of action of 18 to 26 hours

INSULIN ANALOGSUltra short actingUltra short acting

Insulin Lispro Insulin Aspart

Long acting without peak action to Long acting without peak action to simulate normal basal insulinsimulate normal basal insulin Glargine

NEW INSULIN PREPARATIONSInhaled insulin proved to be effective &

will be available within 2 years.Nasal insulin was not successful because

of variable nasal absorption.Oral insulin preparations are under

trials.

ADVERSE EFFECTS OF INSULINHypoglycemiaLipoatrophyLipohypertrophyObesityInsulin allergyInsulin antibodiesInsulin induced edema

PRACTICAL PROBLEMSNon-availability of insulin in poor

countriesinjection sites & techniqueInsulin storage & transferMixing insulin preparationsInsulin & school hoursAdjusting insulin dose at homeSick-day managementRecognition & Rx of hypo at home

DIET REGULATIONRegular meal plans with calorie

exchange options are encouraged.45-50% of required energy to be

obtained from complex carbohydrates, 20-25% proteins, 30% lipids

Distribute carbohydrate load evenly during the day preferably 3 meals & 2 snacks with avoidance of simple sugars.

Encouraged low salt, low saturated fats and high fiber diet.

CHILDRENNUMBER OF CALORIES/DAY = 1000 + (AGE x 100)

EXERCISEDecreases insulin requirement in

diabetic subjects by increasing both sensitivity of muscle cells to insulin & glucose utilization.

It can precipitate hypoglycemia in the unprepared diabetic patient.

It may worsen pre-existing diabetic retinopathy.

MONITORINGCompliance (check records)HBG testsHbA1 every 2 monthsInsulin & meal planGrowth & developmentWell being & life styleSchool & hobbies

Pancreas & Islet Cell TransplantationPancreas transplants are usually

given to diabetics with end stage renal disease.

Islet cell transplants, the ultimate treatment of type 1 diabetes is under trial in many centers in the US & Europe with encouraging results but graft rejection & recurrence of autoimmunity are serious limitations.

IMMUNE MODULATIONImmunosuppressive therapy for

Newly diagnosedProlonged the honey moonFor high risk children

Immune modulating drugs

Nicotinamidemycophenolate

GENE THERAPYBlocks the immunologic attack against

islet-cells by DNA-plasmids encoding self antigen.

Gene encode cytokine inhibitors.Modifying gene expressed islet-cell

antigens like GAD.

PREDICTION OF DIABETESSensitive & specific immunologic

markersGAD Antibodies( Glutamic acid decarboxylase

 antibodies)GLIMA antibodies ( glycated islet cellmembrane–associated protein )IA-2 antibodies ( islet cell antibodies )insulin autoantibodies (IAAs),

Sensitive genetic markers• HLA haplotypes• DQ molecular markers

PREVENTION OF DIABETESPrimary prevention• Identification of diabetes gene• Tampering with the immune system• Elimination of environmental factor

Secondary prevention• Immunosuppressive therapy

Tertiary prevention• Tight metabolic control & good

monitoring

Children and young people with type 1 diabetes should

be offered an ongoing integrated package of care by a

multidisciplinary paediatric diabetes care team. To optimise the effectiveness of care and reduce the risk of complications, the diabetes care team should include members with appropriate training in clinical, educational, dietetic, lifestyle, mental health and foot care aspects of diabetes for children and young people.

POSITIVE DG OF DKAHistory: polydipsia, polyuria• Clinical: acidotic respirationdehydrationdrowsinessabdominal pain/vomiting• Biochemical: high blood glucose on finger-

prick testglucose and ketones in urine

Diabetic ketoacidosis (DKA) NICE guideline

- Primary fluid replacement in DKA should be with isotonic saline, not given too rapidly except in cases of circulatory collapse.

- Bicarbonate should not generally be used in the

management of DKA.- Intravenous insulin should be given by

infusion in cases of DKA.

Potassium replacement should begin early in DKA,with frequent monitoring for the development of

hypokalaemia. add 20 mmol KCl to every 500 ml bag of fluid(40 mmol per litre).

Phosphate replacement should not generally be used in

the management of DKA. In patients whose conscious level is impaired,

considerationshould be given to insertion of a nasogastric tube,

urinarycatheterisation to monitor urine production, andheparinisation. To reduce the risk of catastrophic outcomes in DKA,monitoring should be continuous

British Society for PaediatricEndocrinology and Diabetes (BSPED) recommended

guidelines on diabetic ketoacidosisa fall in plasma sodium concentration during

fluid treatment may be associated with the development of cerebral oedema. Hypotonic saline solutions should therefore not be used, and 0.45% saline with dextrose is now the fluid of choice once the initial phase of treatment with normal saline is complete fluid rehydration should be delivered evenly over 48 hours, and that this practice may reduce the incidence of cerebral oedema

The initial intravenous insulin infusion dose is given as0.1 units/kg/hour. younger children (especially the under 5’s) are

particularly sensitive to insulin and therefore require a lower dose of 0.05 units/kg/hour

Airway Ensure that the airway is patent and if the child is comatose, insert an airway.

If comatose or has recurrent vomiting, insert N/G tube, aspirate and leave on open drainage.

Breathing Give 100% oxygen by face-mask.Circulation Insert IV cannula and take blood samples

(see below).Cardiac monitor for T waves (peaked in hyperkalaemia)If shocked (poor peripheral pulses, poor capillary fillingwith tachycardia, and/or hypotension) give 10 ml/kg0.9% (normal) saline as a bolus, and repeat as necessaryto a maximum of 30 ml/kg.

Once rehydration fluids and potassium are running, blood glucose will already be falling. However, insulin is essential to switch off ketogenesis and reverse the acidosis.

Continuous low-dose intravenous infusion is the preferred method.

solution of 1 unit per ml. of human soluble insulin (e.g.

Actrapid) by adding 50 units (0.5 ml) insulin to 50 ml 0.9% saline in a syringe pump. Attach this using a Y-connector to the IV fluids already running. Do not add insulin directly to the fluid bags.

The solution should then run at 0.1 units/kg/hour (0.1 ml/kg/hour

Algorithm for the management of diabetic

ketoacidosis

ShockReduced peripheral

pulse volumeReduced conscious level

Coma

cerebral oedemamannitol 1.0 g/kg• Restrict IV fluids by 2/3• Move to ITU• CT scan when stabilised

Mild to moderate hypoglycaemia (aware and responds to symptoms):

• Immediately consume rapidly absorbed simple carbohydrate• As symptoms improve or normoglycaemia is restored

consume complex long-actingcarbohydrate• Recheck blood glucose within 15 minutesSevere hypoglycaemia (unable to respond, semi-

conscious/unconscious and requiresassistance):• Use 10% intravenous glucose if in a hospital setting• Use intramuscular glucagon or concentrated oral glucose

solution outside hospital orwhen intravenous access not practical• As symptoms improve or normoglycaemia is restored

consume complex long-acting carbohydrate (if sufficiently awake)

• Repeat blood glucose measurements to check if further glucose is needed

• Seek medical assistance if child/young person fails to respond or symptoms persist for

more than 10 minutes