Diabetes Mellitus in Children Dr Nadeem Zubairi. D.M. Diabetes mellitus is a group of metabolic diseases in which a person has high blood sugar, either.

Diabetes Mellitus in Children

Dr Nadeem Zubairi

D.M.

Diabetes mellitus is a group of metabolic diseases in which a person has high blood sugar, either

because the body does not produce enough insulin, or because cells do not respond to the insulin that is

produced.

This high blood sugar produces the classical symptoms of polyuriapolyuria (frequent urination), polydipsiapolydipsia

(increased thirst) and polyphagiapolyphagia (increased hunger).

© 2004, John Walsh, P.A., C.D.E.

Before Insulin

Before insulin was discovered in 1921, everyone with type 1 diabetes died within weeks to years of its onset

JL on 12/15/22 and 2 mos later

1923Banting and Best AwardedNobel Prize for Discovery And Use of Insulin in theTreatment of IDDM

OLD CLASSIFICATION (1985)

Type 1, Insulin-dependent (IDDM)Type 2, Non Insulin-dependent (NIDDM)

obesenon-obeseMODY

IGTGestational Diabetes

© 2004, John Walsh, P.A., C.D.E.

WHO CLASSIFICATION 2000

Is based on etiology not on type of treatment or age of the patient.Type 1 Diabetes

( autoimmune -cell destruction)

Type 2 Diabetes (defects in insulin secretion or action)

Other specific types

Types of Diabetes in Children

Type 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 diabetesSecondary diabetes e.g. in cystic fibrosis or Cushing syndrome.

EPIDEMIOLOGY Type 1 DM

– Most common metabolic disease in childhood– Annual incidence 15 new cases per 100,000

in children < 18 yrs– Frequency increases with increasing age.– 1: 1400 at age 5 yrs– 1: 400 at age 16 yrs– Males and females equally affected– No correlation with socioeconomic status

Etiology

Type 1 DM usually results from both an inherited risk and external triggers,

Infection,diet .

Type 1 diabetes is an autoimmuneautoimmune disorder in which the body attacks its pancreatic beta cells.

Genetic issuesClear evidence suggests a genetic component in type 1 diabetes mellitus.

Monozygotic twins have a 60% lifetime concordance for developing type 1 diabetes mellitus, although only 30% do so within 10 years after the first twin is diagnosed. In contrast, dizygotic twins have only an 8% risk of concordance, which is similar to the risk among other siblings.

The frequency of diabetes developing in children with a diabetic mother is 2-3% and 5-6% if the father has type 1 diabetes mellitus. The risk to children rises to almost 30% if both parents are diabetic.

Type I – IDDM

Two shared HLA haplotypes

(DR3 + DR4)

12-20% risk

One shared HLA haplotype

(DR3 or DR4)

5-7% risk

No shared HLA haplotypes

1-2% risk

HLA DQ(beta) Asp57

virtual protection

HLA DQ(beta) non-Asp57

100 X increased risk

Environmental factors

Viral infections (most important) probably by initiating or modifying an autoimmune process.( Mumps, coxsackie virus, CMV, congenital rubella)

Dietary factors are also relevantBreastfed infants have a lower risk for Type 1 DM. Some cow's milk proteins (e.g., bovine serum albumin) have antigenic similarities to an islet cell antigen.

Diagnosis

Symptoms of diabetes + casual plasma glucose concentration 11.1 mmol/L ( 200mg/dl).¹≽ ≽

Casual is defined as at any time of the day without regard to time since the last meal.

Or

Fasting plasma glucose 7.0 mmol/L ( 126mg/dl).²≽ ≽

Fasting is defined as no caloric intake for at least 8h.

Or

2h post load glucose 11.mmol/L ( 200mg/dl) during≽ ≽ an OGTT.

Progression to Type 1 DM

Autoimmune destruction

“Diabetes threshold”

Honeymoon

100% Islet loss

Autoimmune markers (ICA, IAA, GAD

Honeymoon Period

In patients with new onset of DM1 who do not have DKA, the beta cell mass has not been completely destroyed.The remaining functional beta cells seem to recover with insulin treatment, and they are again able to produce insulin. When this occurs, insulin requirements decrease, and there is a period of stable blood glucose control, often with nearly normal glucose concentrations. This phase of the disease, known as the honeymoon period, usually starts in the first weeks of therapy and usually continues for a few months at most, but can last 2 years

CLINICAL PRESENTATIONS

Classical symptom triad: polyuria, polydipsia and

weight loss

DKAAccidental diagnosis

COMPLICATIONS OF DIABETES

Acute:DKAHypoglycemiaLate-onset:Retinopathy NeuropathyNephropathyIschemic heart disease &

stroke

© 2004, John Walsh, P.A., C.D.E.

DCCT And Other Studies

ResultsBetter health

Fewer complications

Improved sense of well-being

More flexible lifestyle

StudiesDCCT 1984-1992

EDIC 1996

UKPDS 1978-1998

Kumamoto 1992-2000

Research studies between 1970 and 2000 showed that complications could be prevented by lowering high glucose levels

TREATMENT ELEMENTS

EducationInsulin therapyDiet and meal planningExerciseMonitoringHbA1c every 2-monthsHome regular BG monitoring Home urine ketones tests when

indicated

EDUCATION

Educate child & care givers about: Diabetes Insulin Life-saving skills Recognition of Hypo & DKA Meal plan Sick-day management

ManagementPrinciples of insulin therapy

Varies between individuals and changes over time

The correct dose of insulin is the dose that achieves the best glycemic control without causing obvious hypoglycemia problems and achieving normal growth(height and weight)

Dosage depends on,Age, weight, stage of puberty, duration and phase of diabetes, state of injection sites, nutritional intake and distribution, exercise pattern, daily routine

Hyperglycemia:Microangiopathiccomplications

Hypoglycemia:Neuronal lossPoor school performanceseizures

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

INSULIN ANALOGS

Ultra short actingUltra short acting Insulin Lispro Insulin Aspart

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

Twice daily regimes2 daily injections of a mixture of a short or rapid insulin with an intermediate acting insulin (before meal and before main evening meal).Approximately 1/3 of the total insulin dose is short acting and 2/3 is intermediate.2/3 of the total daily insulin is given in the morning and 1/3 in the evening.

Three injections daily Before breakfast – mixture of rapid or short with

intermediateBefore afternoon snack or evening meal – rapid or short Before bed – intermediate acting

FREQUENTLY USED REGIMES

Insulin Dosage

Prepubertal children usually require

0.7-1.0 IU/kg/day

During puberty, requirements may rise above 1 and even up to 2 IU/kg/day

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.

ADVERSE EFFECTS OF INSULIN

HypoglycemiaLipoatrophyLipohypertrophyObesityInsulin allergyInsulin antibodiesInsulin induced edema

PRACTICAL PROBLEMS

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

TREATMENT MADE EASYInsulin pens & new delivery productsHandy insulin pumpsfine micro needles Simple accurate glucometersFree educational materialcomputer programs for comprehensive management & monitoring

Diet On the standard twice daily regime, food intake is divided into 3 main meals with snacks between meals and before going to bed.

Diet should be high in fibre which will provide a sustained release of carbs.

Type of Food

The following are among the most recent consensus recommendations:Carbohydrates should provide 50-55% of daily energy intake. (No more than 10% of carbohydrates should be from sucrose or other refined carbohydrates.)Fat should provide 30-35% of daily energy intake.Protein should provide 10-15% of daily energy intake.

Activity

Type 1 diabetes mellitus requires no restrictions on activity; exercise has real benefits for a child with diabetes.

Most children can adjust their insulin dosage and diet to cope with all forms of exercise.

The current guidelines are increasingly sophisticated and allow children to compete at the highest levels in sport.

Dreams are the seedlings of realities

FUTURE PROMISESThe cure for IDDM is successful islet

cell transplantation, 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.

DIABETES MELLITUS - TYPE 1MONITORING STRATEGIES

• Self Blood Glucose Monitoring – 2 to 4 / day

• Urine Testing – Ketones

• Glycosylated Hemoglobin - HbA1 C - quarterly

• Blood lipids - annually

• Thyroid function – annually

• Urine micro albumin – quarterly after 5 yr

• Dilated fundoscopy – age 10 yr + 3-5 yr

Diabetic ketoacidosis

Ketoacidosis is a state of uncontrolled catabolism associated with insulin deficiency

Diabetic ketoacidosis tends to occur in individuals younger than 19 years, but it may occur in patients with diabetes at any age.

Criteria

Hyperglycemia: blood glucose >11mmol/L(200mg/dL)

Venous pH<7.3 or bicarbonate <15 mmol/L

Ketonemia and ketonuria

Diabetic ketoacidosisIn the absence of insulin, hepatic glucose production accelerates, and peripheral uptake by tissues such as muscle is reduced.

Rising glucose levels lead to an osmotic diuresis, loss

of fluid and electrolytes, and dehydration.

Plasma osmolality rises and renal perfusion falls.

In parallel, rapid lipolysis occurs, leading to elevated circulating free fatty-acid levels.

The free fatty acids are broken down to fatty acyl-CoA within the liver cells, and this in turn is converted to

ketonebodies within the mitochondria

Diabetic ketoacidosis

Accumulation of ketone bodies produces a metabolic acidosis. Vomiting leads to further loss of fluid and electrolytes.

The excess ketones are excreted in the urine but also appear in the breath, producing a distinctive smell

similar to that of acetone.

Respiratory compensation for the acidosis leads to hyperventilation, graphically described as 'air hunger'.

Progressive dehydration impairs renal excretion of hydrogen ions and ketones, aggravating the acidosis

Diabetic ketoacidosisMostly the causes are

Previous undiagnosed diabetes

Interruption of insulin therapy

The stress of intercurrent illness

Goals of therapyCorrect dehydration

Correct acidosis and reverse ketosis

Restore blood glucose to near normal

Avoid complications of therapy

Identify and treat precipitating event

History Classic symptoms of hyperglycemia

Thirst Polyuria, polydipsia Nocturia

Other symptoms Generalized weakness Malaise/lethargy Nausea/vomiting Decreased perspiration Fatigue Anorexia or increased appetite Confusion

Symptoms of associated infections and conditions Fever Dysuria Chills Chest pain Abdominal pain Shortness of breath

Physical General signs

Ill appearance Dry skin Labored respirations Dry mucous membranes Decreased skin turgor Decreased reflexes

Vital signs Tachycardia Hypotension Tachypnea Hypothermia Fever, if infection

Specific signs Ketotic breath (fruity, with acetone smell) Confusion Coma Abdominal tenderness

Management

1. Fluids- If in shock, initial resuscitation with normal saline. Dehydration

should then be corrected gradually over 48 to 72 hour

using 0.45% Saline - Monitor :

- Fluid input and output- Electrolytes, creatinine and acid-base status regularly- Neurological states

2. Insulin- insulin infusion is started, titrating the dose according to the

blood glucose. Monitor blood glucose regularly.

- aim for gradual reduction of blood glucose .

3. Potassium

Although the initial plasma concentration may be high, it will fall following treatment with insulin and rehydration

High doses (20 to 40 mEq/L) to be added to drips

4. Sodobicarb(used only in selected patients)

-severe acidemia(arterial pH<6.9)in whom decreased cardiac contractility and peripheral vasodilation can further impair tissue function

- life threatening hyperkalemia

- cautiously give 1-2 mmol/kg over 60 min

© 2004, John Walsh, P.A., C.D.E.

COMPLICATIONS OF THERAPY

Main complication is BRAIN EDEMA

TYPE 2 DM IN CHILDREN

Among 10 – 19 yr olds

T2 DM accounts for 33% of all new cases

African Americans – 42%

Caucasians – 10%

Obesity

Acanthosis Nigricans

Natural History of Type 2 DiabetesNatural History of Type 2 Diabetes

Geneticsusceptibility Environmentalfactors

AtherosclerosisHyperglycemiaHypertension

RetinopathyNephropathyNeuropathy

BlindnessRenal failureCHDAmputation

Onset ofdiabetes

Complications Disability

DeathOngoing hyperglycemiaPRE

Obesity Insulin resistance

Risk forDisease

MetabolicSyndrome

Therapy of T2 DM in Children

Reduce calories – weight lossNOT T1 DM diet with high complex CHO

No Between meal snacksNOT T1 DM where hypoglycemia is frequent

Reduce CHO intake

Reduce fat intake

Exercise – increase healthy

life style

Drug treatment early x

TZD = thiazolidinedioneSilverstein JH, Rosenbloom AL.J Pediatr Endcrinol Metab. 2000;13 Suppl 6:1406-1409.

DiagnosisDiagnosisAsymptomatic

Start with insulin and diet, exercise

Diet and exercise

Monthly review, A1C q3mo

>>7%7%

Add metformin

Add metforminAttempt to

wean insulin

Add insulin, TZD, sulfonylurea

BG 250 mg/dL or 12 mmol/LBG 250 mg/dL or 12 mmol/L

Add 3rd agent

<<7%7%

>>7%7%

>>7%7%

<<7%7%

T2 DM vs T1 DMT2 DM T1 DM

Obesity 95% > 85%tile Not Common

+ Family Hx T2 72 – 85% Not Common

Acanthosis Nigricans

60 – 86% 7% all school aged children

Maternal Gestational DM

+ Not Common

IUGR + Not common

T2 DM vs. T1 DM

T2 - DM T1 – DM

Polyuria/dypsia + +

Ketonuria + / - + / -

DKA + / - + / -

Autoimmunity + / - +

Initial insulin Often required Required

Honeymoon + +

Worse @ illness + +

Uncontrolled diabetes can lead to…

Kidney failure

AmputationsLoss of Sensations

Heart disease and strokes

Blindness

Death

© 2004, John Walsh, P.A., C.D.E.

By learning you will teach;

By teaching you will learn.

Latin Proverb

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