19951

8/6/2019 19951

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UPDATE ONUPDATE ON

CHILDHOOD DIABETESCHILDHOOD DIABETESMELLITUSMELLITUS

Abdelaziz Elamin

MD, PhD, FRCPCH

Professor of Child HealthSultan Qaboos University

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DEFINITION The term diabetes mellitus describes

a metabolic disorder of multiple

etiologies characterized by chronichyperglycemia with disturbances of

carbohydrate, fat and protein

metabolism resulting from defects ofinsulin secretion, insulin action or

both.

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DIABETES EPIDEMIOLOGY Diabetes is the most common

endocrine problem & is a major health

hazard worldwide. Incidence of diabetes is alarmingly

increasing all over the globe.

Incidence of childhood diabetes range

between 3-50/100,000 worldwide; inOman it is estimated as 4/100000 peryear.

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OLD CLASSIFICATION (1985)

Type 1, Insulin-dependent (IDDM)

Type 2, Non Insulin-dependent (NIDDM)

obese

non-obese

MODY

IGT Gestational Diabetes

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WHO CLASSIFICATION 2000

Is based on etiology not on typeof treatment or age of the patient.

Type 1 Diabetes

(idiopathic or autoimmune F-celldestruction)

Type 2 Diabetes(defects in insulin secretion or action)

Other specific types

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W

HO CLASSIFICATION/2 Both type 1 & type 2 can be further

subdivided into:

Not insulin requiringInsulin requiring for control

Insulin requiring for survival

Gestational diabetes is a separate entity

Impaired Glucose Tolerance (IGT)indicates blood glucose levels betweennormal & diabetic cut off points duringglucose tolerance test.

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DIAGNOSTIC CRITERIA Fasting blood

glucose level

DiabeticPlasma >7.0 mmol

Capillary >6.0 mmol

IGT

Plasma 6.0-6.9 mmol

Capillary 5.6-6.0 mmol

2 hours afterglucose load

(Plasma or capillary BS) IGT

7.8-11.0

Diabetic level

> 11.1 (200 mg)

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Types of Diabetes in Children

Type 1 diabetes mellitus accounts for>90% of cases.

Type 2 diabetes is increasingly

recognized in children withpresentation like in adults.

Permanent neonatal diabetes

Transient neonatal diabetes Maturity-onset diabetes of the young

Secondary diabetes e.g. in cysticfibrosis or Cushing syndrome.

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MODY Usually affects older children &

adolescents

Not rare as previously considered 5 subclasses are identified, one

subclass has specific mode ofinheritance (AD)

Not associated with immunologicor genetic markers

Insulin resistance is present

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TRANSIENT NEONATAL DIABETES

Observed in both term & preterm

babies, but more common in preterm

Caused by immaturity of islet F-cells

Polyuria & dehydration are prominent,

but baby looks well & suck vigorously

Highly sensitive to insulin

Disappears in 4-6 weeks

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PERMANENT NEONATAL DIABETES

A familial form of diabetes that appear

shortly after birth & continue for life

The usual genetic & immunologicmarkers of Type 1 diabetes are absent

Insulin requiring, but ketosis resistant

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

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TYPE 1 DIABETES: ETIOLOGY

Type 1 diabetes mellitus is anautoimmune disease.

It is triggered by environmentalfactors in genetically susceptibleindividuals.

Both humoral & cell-mediatedimmunity are stimulated.

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GENETIC FACTORS Evidence of genetics is shown in

Ethnic differences

Familial clustering

High concordance rate in twins

Specific genetic markers

Higher incidence with geneticsyndromes or chromosomaldefects

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AUTOIMMUNITY Circulating antibodies against F-cells

and insulin.

Immunofluorescent antibodies &lymphocyte infiltration aroundpancreatic islet cells.

Evidence of immune system activation.

Circulating immune complexes withhigh IgA & low interferon levels.

Association with other autoimmunediseases.

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ENVIRONMENTAL INFLUENCE

Seasonal & geographical variation.

Migrants take on risk of new home.

Evidence for rapid temporal changes.

Suspicion of environmental agentscausing disease which is confirmed by

case-control experimental animalstudies.

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ENVIRONMENTAL SUSPECTS

Viruses

Coxaschie B

MumpsRubella

Reoviruses

Nutrition & dietary factorsCows milk protein

Contaminated sea food

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OTHER MODIFYING FACTORS

The counter-regulatory hormones: glucagon

cortisol, catecholamines

thyroxin,

GH & somatostatin sex hormones

Emotional stress

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ETIOLOGIC MODEL

The etiologic model of type 1diabetes resembles that ofRheumatic fever.

Rheumatic fever was prevented byelimination of the triggering environ.factor ( F-streptococci).

Similarly type 1 diabetes may beprevented by controlling thetriggering factors in high riskpersons.

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CLINICAL PRESENTATIONS

Classical symptom triad:

polyuria, polydipsia and weightloss

DKA

Accidental diagnosis Anorexia nervosa like illness

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DIAGNOSIS

In symptomatic children a randomplasma glucose >11 mmol(200 mg) is diagnostic.

A modified OGTT (fasting & 2h)may be needed in asymptomaticchildren with hyperglycemia if thecause is not obvious.

Remember: acute infections inyoung non-diabetic children cancause hyperglycemia withoutketoacidosis.

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NATURAL HISTORY

Diagnosis & initiation of insulin

Period of metabolic recovery

Honeymoon phase

State of total insulindependency

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METABOLIC RECOVERY

During metabolic recovery the patient may

Develop one or more of the following:

Hepatomegaly Peripheral edema

Loss of hair

Problem with visual acuity

These are caused by deposition ofglycogen & metabolic re-balance.

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HONEYMOON PERIOD

Due to F-cell reserve optimalfunction & initiation of insulintherapy.

Leads to normal blood glucoselevel without exogenous insulin.

Observed in 50-60% of newly

diagnosed patients & it can last upto one year but it always ends.

Can confuse patients & parents ifnot educated about it early.

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COMPLICATIONS OF DIABETES

Acute:

DKA

Hypoglycemia

Late-onset:

Retinopathy

NeuropathyNephropathy

Ischemic heart disease & stroke

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TREATMENT GOALS Prevent death & alleviate symptoms

Achieve biochemical control

Maintain growth & development

Prevent acute complications

Prevent or delay late-onset

complications

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TREATMENT ELEMENTS

Education

Insulin therapy

Diet and meal planning

Monitoring

HbA1c every 2-months

Home regular BG monitoring

Home urine ketones tests whenindicated

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EDUCATION Educate child & care givers about:

Diabetes

Insulin

Life-saving skills

Recognition of Hypo & DKA

Meal plan

Sick-day management

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INSULIN

A polypeptide made of 2 F-chains.

Discovered by Bants & Best in 1921.

Animal types (porcine & bovine) wereused before the introduction of human-

like insulin (DNA-recombinant types).

Recently more potent insulin analogsare produced by changing aminoacid

sequence.

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FUNCTION OF INSULIN Insulin being an anabolic

hormone stimulates protein &

fatty acids synthesis. Insulin decreases blood sugar

1. By inhibiting hepatic glycogenolysisand gluconeogenesis.

2. By stimulating glucose uptake,utilization & storage by the liver,muscles & adipose tissue.

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TYPES OF INSULIN

Short acting (neutral, soluble, regular)Short acting (neutral, soluble, regular)

Peak 2-3 hours & duration up to 8 hours

Intermediate 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

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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.

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INSULIN REGIMENS

Twice daily: either NPH alone orNPH+SI.

Thrice daily: SI before each mealand NPH only before dinner.

Intensive 4 times/day: SI beforemeals + NPH or Glargine at bed

time. Continuous s/c infusion using

pumps loaded with SI.

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INSULIN ANALOGS

Ultra short actingUltra short acting

Insulin Lispro

Insulin Aspart

Long acting without peak actionLong acting without peak actionto simulate normal basal insulinto simulate normal basal insulin

Glargine

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NEW INSULIN PREPARATIONS

Inhaled insulin proved to beeffective & will be available within

2 years.

Nasal insulin was not successfulbecause of variable nasal

absorption. Oral insulin preparations are

under trials.

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ADVERSE EFFECTS OF INSULIN

Hypoglycemia

Lipoatrophy

Lipohypertrophy

Obesity

Insulin allergy

Insulin antibodies

Insulin induced edema

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PRACTICAL PROBLEMS

Non-availability of insulin in poorcountries

injection sites & technique Insulin storage & transfer

Mixing insulin preparations

Insulin & school hours

Adjusting insulin dose at home

Sick-day management

Recognition & Rx of hypo at home

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DIET REGULATION

Regular meal plans with calorieexchange options are encouraged.

50-60% of required energy to be

obtained from complex carbohydrates. Distribute carbohydrate load evenly

during the day preferably 3 meals & 2snacks with avoidance of simplesugars.

Encouraged low salt, low saturated fatsand high fiber diet.

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EXERCISE

Decreases insulin requirement indiabetic subjects by increasing

both sensitivity of muscle cells toinsulin & glucose utilization.

It can precipitate hypoglycemia in

the unprepared diabetic patient. It may worsen pre-existing

diabetic retinopathy.

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ADVANCES IN MONITORING

Smaller & accurate meters forintermittent BG monitoring

Glucowatch continuous monitoringusing reverse iontophoresis tomeasure interstitial fluid glucoseevery 20 minutes

Glucosensor that measures s/ccapillary BG every 5 minutes

Implantable sensor with high & lowBG alarm

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ADVANCES IN MANAGEMENT

Better understanding of diabetesallows more rational approach to

therapy.

Primary prevention could bepossible if the triggering factors are

identified.

The DCCT studies proves beyonddoubt that chronic diabetic

complication can be controlled or

prevented by strict glycemic control.

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TREATMENT MADE EASY

Insulin pens & new deliveryproducts

Handy insulin pumps

fine micro needles

Simple accurate glucometers

Free educational material

computer programs forcomprehensive management &monitoring

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TELECARE SYSTEMS

IT has improved diabetes care

Internet sites for education &support

Web-based systems for telecareare now available. The patientfeeds his HBGM data and get the

physician, nurse & dietician adviceon the required modification todiet & insulin treatment.

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PITFALLS OF MANAGEMENT

Delayed diagnosis of IDDM

The honey-moon period

Detection & treatment of NIDDY

Problems with diagnosis &

treatment of DKA & hypoglycemia

Somogi¶s effect (dawnphenomenon) may go

unrecognized.

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FUTURE PROMISES

The cure for IDDM is successful islet celltransplantation, which will be available

in the near future.

Primary prevention by a vaccine or drug

will be offered to at risk subjects

identified by genetic studies.

Gene modulation therapy for

susceptible subjects is a promising

preventive measure.

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Pancreas & Islet Cell Transplantation

Pancreas transplants are usuallygiven to diabetics with end stagerenal disease.

Islet cell transplants, the ultimatetreatment of type 1 diabetes isunder trial in many centers in theUS & Europe with encouragingresults but graft rejection &recurrence of autoimmunity areserious limitations.

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IMMUNE MODULATION

Immunosuppressive therapy for

Newly diagnosed

Prolonged the honey moon

For high risk children

Immune modulating drugs

Nicotinamide

mycophenolate

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GENE THERAPY

Blocks the immunologic attackagainst islet-cells by DNA-

plasmids encoding self antigen. Gene encode cytokine inhibitors.

Modifying gene expressed islet-

cell antigens like GAD.

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PREDICTION OF DIABETES

Sensitive & specific immunologicmarkers

GAD AntibodiesGLIMA antibodies

IA-2 antibodies

Sensitive genetic markers HLA haplotypes

DQ molecular markers

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Dreams are the seedlings

of realities

19951

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