Treatment of children and adolecents with diabetes

Posted on November 27, 2009

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Posted by at on November 27, 2009

Treatment of children and adolecents with diabetes

Written by
Dr. Birthe S Olsen, Consultant Paediatrician
Dr. Henrik Mortensen, Chief Physician, Senior Paediatric Endocrinologist

From Department of Paediatrics, Glostrup University Hospital, Copenhagen, Denmark

Childhood diabetes
• 90% Type 1 diabetes
• Absolute or relative insulin deficiency
• Auto-immune process
• Pancreatic beta-cell destruction
Aetiology
• Genetic susceptibility:
• HLADR3, HLADR4 : risk increased
• HLADR2 : risk reduced
• Environmental factors:
• viral factors
• nutritional factors

Epidemiology
• Most common endocrine disease in childhood
• Highest incidence in Finland and Sardinia
• Highest incidence in males
• Highest incidence at 10–12 years and 5–7 years
• Increasing incidence in very young children (0–4 years)
• Seasonality
• More common in families where father has diabetes

Pre-diabetes phase
• Gradual destruction of beta-cells
• Development of auto-antibodies:
• ICA
• IAA
• GADA

Prevention
• Primary intervention:
• aimed at reducing the prevalence of a given condition in susceptible individuals
• Example: cow’s milk exclusion in infancy
• Secondary intervention:
• aimed at early detection of a given disease and stopping or slowing further progression
• Example: ENDIT study
• Tertiary intervention:
• aimed at preventing complications associated with a disease
• Example: improvement in glycaemic control, screening for complications.

Management – primary goals
• To ensure that insulin is available for all children
• To ensure that the child gradually takes over the responsibility for the disease (self-care)
• To ensure optimum glycaemic control
• To ensure freedom from diabetic complications
• To ensure normal growth and development

Symptoms and signs:
• polydipsia
• polyuria
• night-time incontinence
• loss of weight
• irritability
• abdominal pain
• visual disturbances
• frequent infections

The newly-diagnosed child
• Diagnosis:
• fasting blood-glucose concentration > 7.7 mmol/l
• random blood-glucose concentration > 11 mmol/l
• glucosuria
• ketonuria
• ketoacidosis
• Differential diagnosis:
• inflamed appendix
• pneumonia
• urinary tract infection
The multi-disciplinary team
• The cornerstone in childhood diabetes management:
• a paediatric endocrinologist
• a specialised nurse
• a specialised dietician
• a chiropodist
• a specialised social worker
• a childhood psychologist
• close collaboration with other relevant departments

The multi-disciplinary team
• The team should…
• have common attitudes and philosophy
• meet regularly for discussion and education
• develop written material dealing with daily-life and emergency issues
• encourage research in childhood diabetes
• attend in-service training

Diabetes education 1
• Initial ‘survival’ education:
• the causes of diabetes
• insulin management
• injection technique
• blood glucose measurements
• acceptable blood glucose values
• advice about hypo- and hyperglycaemic episodes
• dietary advice

Diabetes education 2
Over the next months and years a more comprehensive education programme, adjusted to the age and maturity of the child:
• aetiology and pathology
• injection devices and methods
• blood-glucose monitoring
• diet
• insulin adjustments
• hypoglycaemia
• insulin-treatment
• hyperglycaemia

• sick-day management
• sport
• alcohol
• drug abuse
• travelling
• gynaecological issues
• complications

Diabetes education 3
• The knowledge and skills of the child should be regularly assessed
• Re-education should be performed accordingly
Treatment
• At diagnosis
• Remission phase
• Long-term

• Insulin:
• subcutaneous
• multiple dose rapid-acting insulin before meals, or
• combination of rapid- and intermediate-acting insulin twice daily
• insulin requirements may exceed 1.5–2 IU/kg/24 hours

• Potassium:
• < 12 years 750 mg KCl for 3–4 days
• > 12 years 1500 mg KCl for 3–4 days

• hospital stay as short as possible
• in paediatric setting
• frequent visits to out-patient clinic
• 24-hour hot-line service
• home and institution visits

Always managed at hospital in case of:
• ketoacidosis
• severe dehydration
• very young age
• infection
• psychosocial problems
• language and cultural difficulties

The remission phase
• Duration from weeks to months
• Shorter in young children
• Blood glucose values between 4–8 mmol/l
• Decreasing insulin requirements < 0.5 IU/kg/24 hours
• One daily insulin injection is often sufficient
• Insulin injections should not be abandoned

Partial remission phase
Long-term management
• Twice daily or multiple insulin injections
• Regular blood glucose measurements
• At least 4 visits to out-patient clinic every year
• Instant HbA1c measurements at every visit
• Height and weight measurements at every visit
• Physical examination with pubertal staging every year
• Regular screening for diabetes related complications

Insulin
• All children with Type 1 diabetes must have insulin
• Consequences of long-term insulin omission:
• growth retardation
• delayed puberty
• poor metabolic control
• microvascular complications
• short life expectancy
• poor quality of life

Insulin types and duration of action
Insulin
preparation

• Short-acting
• Intermediate-acting
• Premixed insulin 10/90
• Premixed insulin 20/80
• Premixed insulin 30/70
• Premixed insulin 40/60
• Premixed insulin 50/50
• Rapid-acting insulin analogue

Short-acting insulin
• Clear solution
• Indications for use:
• daily management of diabetes, alone or in combination with intermediate-acting insulin
• hyperglycaemia
• sick-day management
• intravenous therapy

Intermediate-acting insulin
• Cloudy solution (should be thoroughly mixed before use)
• Indications for use:
• daily management of diabetes, alone or in combination with short-acting insulin

Pre-mixed insulin
• Cloudy solution (should be thoroughly mixed before use)
• Indications for use:
• daily management of diabetes, alone or in combination with short-acting insulin

Rapid-acting insulin (Insulin Aspart)
• Clinical benefits
• improved metabolic control compared with human soluble insulin
• fewer hypoglycaemic episodes
• no post-prandial hypoglycaemia
• rapid onset of action
• short duration of action
• Better quality of life and improved conveinence

Rapid-acting insulin (Insulin Aspart)
• Patient targeting:
• Newly diagnosed children and adolecents with diabetes
• Children and adolecents currently on basal/bolus regimens
• Children and adolecents poorly controlled diabetes on twice daily therapies

Storage of insulin
• Stable at room temperature for weeks
• Should not be exposed to temperatures > 25ºC or under freezing point
• Unused vials and cartridges should be stored in the refrigerator
• Should never be exposed to sunlight
• Should never be frozen

Injection sites
Short acting insulin:
• injected subcutaneously into the abdomen at a 45° angle

Intermediate-acting and pre-mixed insulins:
• injected subcutaneously in the front of the thighs or into the buttocks at a 45° angle

Insulin absorption
• Factors influencing insulin absorption:
• injection site
• injection depth
• insulin type
• insulin dose
• physical exercise
• skin temperature

Insulin requirements
• Remission period < 0.5 IU/kg/24 hours
• Pre-pubertal period 0.6–1.0 IU/kg/24 hours
• Pubertal period 1.0–2.0 IU/kg/24 hours

Insulin regimens
• should be adjusted to age, maturity and motivation
• should be as simple as possible

Children for multiple injection therapy:
• should be selected carefully
• should understand the relationship between insulin, food and physical exercise
• should be motivated and have family support
• should be willing to measure blood glucose several times every day
• should be willing to inject insulin at school
Insulin regimens
• Most widely used insulin regimens:
• twice-daily injections, mixture short and intermediate, before breakfast and the evening meal
• three daily injections, mixture short and intermediate before breakfast, short-acting before the evening meal and intermediate-acting before bed
• short-acting insulin before main meals, intermediate before bed

Insulin distribution
Twice daily injection regimen:
• 2/3 of daily dose before breakfast,
• 1/3 before supper
• both 2/3 intermediate-acting and 1/3 short-acting insulin
Three-times daily injection regimen:
• 40–50% before breakfast (2/3 intermediate-acting and 1/3 short-acting)
• 10–15% short-acting before supper
• 40% intermediate-acting before bed.
Multiple injection regimen:
• 30–40 % (intermediate) before bed
• the rest (short-acting) before main meals

Insulin adjustments
Twice-daily injection regimen:
• Blood glucose high: Dose of insulin to increase
• Before breakfast or  overnight Evening intermediate-acting
• Before lunch Morning short-acting
• Before dinner Morning intermediate-acting
• Before bed Evening short-acting
• Blood glucose low: Dose of insulin to decrease
• Before breakfast or overnight Evening intermediate-acting
• Before lunch Morning short-acting
• Before dinner Morning intermediate-acting
• Before bed Evening short-acting

Three-times daily injection regimen:
• Blood glucose high: Dose of insulin to increase
• Before breakfast or overnight Evening intermediate-acting
• Before lunch Morning short-acting
• Before dinner Morning intermediate-acting
• Before bed Evening short-acting
• Blood glucose low: Dose of insulin to decrease
• Before breakfast or overnight Evening intermediate-acting
• Before lunch Morning short-acting
• Before dinner Morning intermediate-acting
• Before bed Evening short-acting

Basal-bolus (multiple injection) regimen:
• Blood glucose high: Dose of insulin to increase
• Before breakfast or overnight Evening intermediate-acting
• Before lunch Morning short-acting
• Before dinner Lunch time short-acting
• Before bed Evening short-acting
• Blood glucose low: Dose of insulin to decrease
• Before breakfast or overnight Evening intermediate-acting
• Before lunch Morning short-acting
• Before dinner Lunch time short-acting
• Before bed Evening short-acting

Diet
Nutritional advice should take into consideration:
• individual requirements
• local customs
• family dietary habits
• General recommendations:
• eat a broad variety of food
• eat plenty of bread, cereals, vegetables and fruit
• eat only small amounts of sugar
• in young children the fat intake should not be restricted
• older children and adolescents should eat a low fat diet
• choose food with small amounts of salt
• encourage breast-feeding at least till six months of age

Diet – principles
Number of meals:
• 3 main meals
• 3 snacks
• adapted to age, physical activity and insulin regimen
Energy intake:
• 1000 calories (4180 Kj) + 100 calories/year of age
• 50–55% of energy from carbohydrates

• 30% of energy from fat

• 15–20% of energy from protein
Glycaemic index (GI):
• carbohydrate ranking system
• based on post-prandial blood glucose response
• low GI = slow, sustained blood glucose response (e.g. rice, pasta)
• high GI = rapid and high blood-glucose response (e.g. white bread, candy/sweets, cornflakes, honey, sugar)

Carbohydrate exchange system:
• based on the carbohydrate content and not the weight of the food
• makes it easy to exchange carbohydrate containing food elements (e.g. 15 g carbohydrates in candy for 15 g carbohydrates in fruit)
• one exchange usually contain 10–15 g carbohydrate
Exercise
• Increases insulin sensitivity
• Improves the physical state
• Reduces the risk of cardiac diseases
• Reduces the risk of hypertension
• Does not improve metabolic control
• Increases the risk for hypoglycaemia
• Measure blood glucose before, during and after physical exercise
• Increased risk for hypoglycaemia 12–40 hours after strenuous physical exercise
• Reduce short-acting insulin accordingly

• Blood glucose before bedtime should be > 10–12 mmol/l

Hypoglycaemia
• Blood glucose < 3 mmol/l
• Mild (grade 1): recognised and treated orally by the patient
• Moderate (grade 2): treated orally, with help from someone else
• Severe (grade 3): unconscious or having fits – nothing by mouth

• Causes:
• strenuous exercise
• missed meals
• injection errors
Hypoglycaemia, symptoms

Neurogenic:
• sweating
• hunger
• tremor
• pallor
• restlessness

Neuroglycopenic:
• weakness
• headache
• change in behaviour
• tiredness
• visual and speech disturbances
• vertigo
• lethargy
• confusion
• fits and unconsciousness

Hypoglycaemia – treatment
Mild hypoglycaemia (Grade 1):
• 10–20 g glucose tablets, juice or sweet drinks
• 1–2 slices of bread

Moderate hypoglycaemia (Grade 2):
• 10–20 g glucose tablets
• 1–2 slices of bread

Severe hypoglycaemia (Grade 3):
Outside hospital:
• children < 10 years: 0.5 mg glucagon i.m.
• children > 10 years: 1.0 mg glucagon i.m.
• In hospital:
• bolus glucose (20%) 1 ml/kg over 3 min followed by
• glucose (10%), 0.2 ml/kg/min

Ketoacidosis
Severity degree:
• Mild ketoacidosis bicarbonate > 16 and < 22 mmol/l
• Moderate ketoacidosis bicarbonate > 10 and < 16 mmol/l
• Severe ketoacidosis bicarbonate < 10 mmol/l

Characterised by:
• absolute insulin deficiency
• increased level of counter regulatory hormones

Aetiology:
• newly diagnosed
• infections
• insulin omission

Ketoacidosis – symptoms
Symptoms and signs:
• dehydration
• vomiting
• loss of weight
• Kussmaul respirations
• acetone smell
• impaired sensorium
• shock

Ketoacidosis – diagnosis
Clinical appearance
• Hyperglycaemia
• Ketonuria
• Ketonaemia
• Plasma bicarbonate < 22 mmol/l

Treatment: Fluid
Due to the risk for overhydration:
• fluid volume in the first 24 hours should not exceed 4 l/m2
• rehydration over 24–36 hours
• Initiate treatment with isotonic 0.9 % saline:
• 1st hour : 20 ml/kg body weight (previous)
• 2nd hour : 10 ml/kg body weight
• 3rd hour onwards : 5 ml/kg body weight
• When blood glucose levels are below 12 mmol/l:
• 5–10 % glucose solution

Treatment: Insulin
Low-dose insulin regimen:
• short-acting insulin
• intravenously
• bolus or continuous infusion
• 0.1 IU/kg/hour
• Ideal blood-glucose fall:
• maximal 4–5 mmol/l
• Until acidosis is corrected:
• adjust insulin and fluid to blood glucose level between 5–15 mmol/l
Treatment: Potassium
• DKA is always accompanied by severe potassium deficiency
• Treatment:
• initially add 20 mmol KCl to 500 ml fluid
• adjust potassium replacements to plasma potassium level:
Treatment Sodium:
• measured level low due to dilution
• only correction if values are below 120 mmol/l
• if values are above 160 mmol/l (hypernatriaemic state)
• rehydrate over 48–72 hours
• Bicarbonate:
• only in very sick children with severe ketoacidosis (pH < 7.0)
• recommended dose 1–2 mmol/kg
• ½ of the dose over 30 minutes and ½ over 1-2 hours
• Hazards to bicarbonate treatment:
• precipitation of hypokalaemia
• paradoxically exacerbating of CNS acidosis
• cerebral oedema

Sick-day management
Basis for sick-day management at home:
• insulin should never be omitted
• frequent blood glucose measurements
• frequent urine testing for ketone bodies
• close contact to the diabetes team
• Situations where admittance to hospital is indicated:
• persisting vomiting
• increasing ketone bodies in the urine
• increasingly sick child
• abdominal pain
• non-compliance and psycho-social problems
• language and cultural difficulties
• very young age (< 2 years)
Situations with high fever, high blood-glucose and ketonuria:
• most often caused by bacterial infections
• seek and treat the infection focus
• give frequent subcutaneous injections of short-acting insulin
• continue treatment until ketone bodies have disappeared
• give glucose containing food or drinks to maintain acceptable blood glucose values
• encourage the child to drink plenty of fluids
Situations with low-grade fever, low blood-glucose and ketonuria
• most often caused by viral infections
• associated with anorexia, vomiting and diarrhoea
• reduce short- and intermediate- acting insulin according to blood glucose values
• give glucose containing food or drinks to maintain acceptable blood glucose values
• encourage the child to drink plenty of fluids
Minor surgery (duration < 3 hours
Insulin:
in the morning intermediate-acting insulin, 1/2 to 2/3 of total daily dose
• if blood glucose is above 20 mmol/l supply with a small dose short-acting insulin
in the evening give intermediate-acting insulin, 1/3 of daily dose
• Fluid:
• glucose 5% intravenously, volume according to age
Blood glucose monitoring:
• every 1–2 hours
• values between 10–14 mmol/l

Major surgery (duration > 3 hours)
• Insulin and fluid:
• infusion solution containing 5% glucose and 20 mmol/l sodium chloride (maintenance volume)
• 50 IU short-acting insulin in 500 ml 0.9 % saline by separate drip infusion 0.5 ml = 0.05 IU/kg/hour
• Blood glucose monitoring:
• every 1–2 hours
• values between 6–14 mmol/l
• if < 5 mmol/l reduce infusion rate
• continue infusion therapy until food intake is re-established

HbA1c:
• reflects average blood glucose level over last 4–6 weeks
• should be measured and available at every out-patient clinic visit
• Home blood glucose (HBG) measurement:
• ideally before breakfast, lunch, evening meal and bedtime
• before, during and after physical exercise
• during intercurrent illnesses
• if hypo- or hyperglycaemia is suspected
• following hypoglycaemia
• after changing insulin dose
• frequency of HBG should be adjusted to age, insulin regimen and acceptance of the child
Urine testing:
• ketone testing in case of fever and high blood glucose

• Goals:
• Well-adjusted children/adolescents with normal growth and development
• HbA1c between 7–9%
• Less than 10–20 severe hypoglycaemia episodes and ketoacidosis per 100 patient years
• Post-prandial blood glucose values below 10–12 mmol/l
• Pre-prandial blood glucose values between 4–8 mmol/l
• Glycaemic goals less strict for very young children
• Goals realistic and individualised in puberty

Microvascular complications in kidneys, eyes and nerves:
• closely related to poor long-term metabolic control
• occur from puberty
• preceded by subclinical changes
• can be delayed or prevented by good metabolic control
Diabetic nephropathy:
• leading cause of increased morbidity and mortality in Type 1 diabetes
• preceded by microalbuminuria (albumin excretion rate > 20 µg/min)
• prevalence in adolescence 5–20%
• correlated with long-term metabolic control
• long diabetes duration
• elevated arterial blood pressure
• genetic susceptibility

Diabetic nephropathy
Annual screening:
• after 5 years’ diabetes duration in pre-pubertal children
• after 2 years’ diabetes duration in adolescents
Screening method:
• albumin excretion rate calculated from 3 night-time urine collections
• Microalbuminuria treatment:
• improved long-term metabolic control
• normalising arterial blood pressure
• smoking discouraged
• ACE-inhibition

Diabetic retinopathy:
• leading cause of visual loss and blindness in working-age population
• prevalence in adolescence: 10–80%
• correlated with long-term metabolic control
• long diabetes duration
• elevated arterial blood-pressure
• genetic susceptibility

• Background retinopathy:
• not vision threatening
• stable for many years

• Proliferative retinopathy:
• vision-threatening
• new vessels
• retinal retraction
Annual screening:
• after 5 years’ diabetes duration in pre-pubertal children
• after 2 years’ diabetes duration in adolescents
Screening method:
• ophthalmoscopy
• fundus photography
• fluorescein angiography
• Retinopathy treatment:
• improved long-term metabolic control
• normalising arterial blood pressure
• laser therapy in case of proliferative retinopathy

• peripheral and autonomic
• rare in childhood and adolescence
• preceded by subclinical abnormalities
• correlated with poor long-term metabolic control
• correlated with long diabetes duration
• correlated with older age
• correlated with higher Tanner stage
• correlated with male sex
Annual screening:
• from puberty
• Screening method:
• ankle reflexes
• sensation (temperature discrimination)
• non-invasive test of nerve function (biothesiometry)
• Neuropathy treatment:
• improved long-term metabolic control
Insulin insensitivity
• Poor metabolic control
• Insulin omission
• Overweight
• Eating disorders
• Psychosocial problems
• Microvascular complications

Adolescence

Treatment strategies:
• non-threatening open-minded atmosphere
• patience
• respect
• flexible appointment times
• opportunity to meet other adolescents with diabetes
• planned transition to adult setting
• parental involvement

Risk-taking behaviour
• Alcohol:
• impairs gluconeogenesis
• associated with severe hypoglycaemia
• Advice:
• drink in moderation
• measure blood glucose (HBG) regularly
• eat complex carbohydrates while drinking alcohol
• measure HBG before going to bed
• if HBG is not measured always eat extra food before bedtime
• make sure that your friends are aware of your diabetes
• always wear your diabetes amulet when going to parties
• Smoking:
• harmful to the health of all people
• associated with increased risk for microvascular complications
• is expensive
• is addictive
• Drug abuse:
• should be considered in connection with other risk-taking behaviour

Gynaecological issues
Menstruation:
• may be irregular due to poor metabolic control
• may be accompanied by high blood glucose levels
Oral contraceptives with low-dose oestrogen:
• safe for most adolescents with diabetes
• may be accompanied by insulin resistance
• should not be used in cases of arterial hypertension
• Condoms:
• safe contraceptive method
• protects against sexually transmitted diseases

School
• All children should be attending school
• Academic expectations should be the same
• Teachers and school nurse should be informed about general rules and emergency situations
• Written material about diabetes should be handed out to school staff
• A close communication should exist between home and school

Camps, school and travelling
Travelling
• Appointment in the out-patient clinic 4–6 weeks before travel
• Improve metabolic control, if necessary
• Make sure that the family is capable of treating hypo- and hyperglycaemic episodes
• Make sure that the family is informed about sick-day management
• Make sure that travel health insurance is valid

Travelling
• Bring:
• introduction letter
• sufficient insulin, needles, blood glucose testing material and glucagon
• blood glucose meters and extra batteries
• extra food and drink

• Long flights:
• stick to the ‘home-time’ and normal routines
• 6-hourly injections of short-acting insulin
Psychosocial problems in childhood diabetes:
• the illness imposes major demands on the child and family
• pre-existing problems may interfere with the patients compliance
• different psychological problems may emerge in different age-groups
Parents:
in shock at diagnosis
• Young children:
• needle-phobia and eating problems
• Adolescents:
• poor compliance, insulin omission, eating disorders
• The team should:
• look for these problems already from diagnosis
• take care that early counselling is initiated

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