2. Introduction
Def.:- chronic, metabolic syndrome characterized by
hyperglycemia as a cardinal biochemical feature
Type 1 diabetes is the most common endocrine disease
of childhood and adolescence
Type 2 diabetes may also occur in childhood.
There are other types of diabetes – MODY 1-6,
acromegaly, Cushing's, post pancreatitis,
hemochromatosis, hyperthyroidism, glucagonoma,
drug related e.g. steroids, pentamidine
4. Introduction
Commonest type in paediatrics
Results from autoimmune destruction of the
pancreatic β-cell with resultant absolute deficiency of
insulin
Previously called IDDM or juvenile DM
Commoner in whites but least common in Chinese . In
high incidence areas 2 peaks at 4-6 yrs and 10-14 yrs.
Incidence increases with distance from equator
5.
6. Etiology
The disease results from interaction between environment
and genetics in a susceptible individual.
This results in progressive β-cell damage with symptoms
appearing after 90% damage
Genetic evidence: 2-3% chance if mother has DM, 5-6% if
paternal DM and 30% both parents.
Monozygotic twins lifetime concordance rate- 60% yet
dizygotic risk or other sibling rate 8%.
In the monozygotic the appearance occurring after onset
in one in 10 yrs is 30%
7. Etiology
HLA II DR3 and DR4 are associated with DM
Environmental factors thought to include viruses
(paradox- IDDM commoner in low infection
communities), cow milk proteins, chemicals , lack of
UV light exposure, Vit. D deficiency
Other causes include pancreatic damage of varied
causes
There is increased risk in Downs, Klinefelter’s, Prader-
Willi and Turner’s syndromes
8. Prognosis
With good control one may lead a full normal life, but
it is calculated that overall type 1 DM reduces life
expectancy by 13-19 yrs
Long term complications include: Retinopathy
Cataracts, Gastro paresis, Hypertension, Progressive
renal failure, Early coronary artery disease, Peripheral
vascular disease. Peripheral and autonomic
neuropathy and Increased risk of infection
9. Clinicals
Hyperglycemia, glycosuria, polydipsia, polyuria,
weight loss, blurry vision, malaise, DKA, and increased
susceptibility to infections
Clinical exam may be normal with mild wasting and
dehydration. May present with retinopathy,
necrobiosis
10. Differential diagnosis
Type 2 diabetes mellitus
MODY
Psychogenic polydipsia
Nephrogenic diabetes insipidus
High-output renal failure
Transient hyperglycemia with illness and other stress
Steroid therapy
Factitious illness (Munchhausen syndrome)
11. Diagnostics
Blood sugar: a random blood sugar > 11.1mmol/l and
fasting blood sugar >6.7 mmol/l is diagnostic in the
absence of transient illness or stress induced
hyperglycemia
An oral glucose tolerance test may be required if it is
thought that the hyperglycemia is due to transient
causes.
Glycosuria suggests but is not diagnostic of DM.
12. Diagnostics
Micro-albuminuria is early indicator of DM nephropathy.
Ketonuria occurs in DKA but may also occur in starvation
Glycated Hb: this results from non-enzymatic reaction
between glucose and Hb. It is useful in monitoring
medium-long term glycemic control’. A level of HbA1c >
6.5% is indicative of diabetes. In pediatrics it is suggested
that a level less than 7.5% indicates good control.
13. Treatment
Type 1 DM requires insulin therapy
Close monitoring to ensure glycemic control
Insulin therapy ideally should be tailored to meet individual
needs
4 basic types of insulin- ultra-short acting, short acting
(regular-soluble), intermediate and long acting insulin
Usual daily dose in a child with no insulin reserve is 0.7 u/kg
in pre-pubertals, 1u/kg in mid-puberty and 1.2u/kg in end-
puberty ( this doses may be slightly reduced in newly
diagnosed due to honeymoon effect)
14. Possible long term insulin treatment
regimes
Twice daily dosing with a combination of
short/intermediate insulins
OD or BD doses of intermediate/long insulins + short
acting insulins with each meal.
Combination of above 2 with morning dose of mixed
afternoon pre-meal short and evening intermediate/
long acting insulin
Continuous sub-cutaneous insulin using insulin
infusion pump
16. Introduction
More common in adults but incidence increasing in
children.
Poly-genic disease aggravating factors like low
physical activity and high caloric and high lipid diet.
In type 2 DM there is increased insulin resistance of
skeletal muscle, enhanced hepatic glucose production
and reduce glucose –induced insulin secretion. Insulin
deficiency is not absolute so may survive without
insulin therapy.
17. Risk factors of type 2 DM
Obesity and inactivity
High or low birth weight
History of type 2 DM in 1st or 2nd degree relatives
History of maternal gestational DM
Race (eg native american,blacks and hispanics)
Not breast-fed in infancy
Age 12-16 years ( age associated with relative puberty
associated insulin resistance)
18. Signs and symptoms typically
differentiating from type 1
Insidious onset- initially glucose intolerance
progressing over time to frank DM
Common in obesity from high risk race
Family history of type 2 DM
Signs of insulin resistance: hypertension, polycystic
ovarian syndrome, acanthosis nigricans
Other signs may be similar e.g. retinopathy, and
nephropathy which seems to appear earlier in type 2.
19. Diagnosis
Raised blood sugars and glycosuria just as in type 1
However in type 2 there are clinical features
associated with insulin resistance e.g. obesity and
hypertension.
In type 2 DM fasting C-peptide and insulin levels
usually raised and autoimmune markers are negative
unlike in type 1 e.g. glutamate decarboxylase (GAD)
and islet cell antibodies
20. Treatment of type 2 DM
If initially patient has ketosis and very high glucose
levels it is better to start insulin therapy as it may be
difficult to distinguish type 1 and 2.
If less severe or surely confirmed it is treated by
lifestyle modification and oral hypoglycaemic,
(currently only metformin) to maintain glycaemia and
HbA1c < 7%
Control of serum lipids and blood pressure
21. Long term complications of poor
glycemic control
Nephropathy: prevented by tight glucose control.
Early detection by microalbuminuria which progresses
to overt proteinuria. It is controlled by good glycemic
control, tight high BP control use of ACE inhibitors
and protein restriction.
Neuropathy: peripheral and autonomic nerve damage
due to hyperglycemia. Prevented by tight control, use
of aldolase reductase inhibitors, anti-oxidants and
anti-convulsants.
22. Complications ct
Retinopathy: higher incidence in type 1. leading cause
of blindness. Frequent eye reviews advised, tight
glycemic control advised. Treatment is with laser
therapy and vitrectomy
Macrovascular disease: hypertension is commonest
manifestations. Is treated with BP control and statins
24. Introduction
Metabolic syndrome characterised by hyperglycemia,
ketosis and acidosis
mild DKA= pH < 7.30 or bicarb < 15 mmol/L
moderate = pH < 7.20 or bicarb < 10 mmol/L
severe = pH < 7.10 or bicarb < 5 mmol/L
Presentation: Often insidious, Fatigue and malaise,
Nausea/vomiting, abdominal pain, Polydipsia,
Polyuria, Polyphagia, Weight loss, Fever
25. Pathology
Low insulin levels results in hyperglycemia that causes
osmotic diuresis with hypovolemia that causes tissue
hypoperfusion and lactic acidosis.
Glucagon excess increases lipolysis and proteolysis
whose end-products are keto-acids.
Diuresis depletes total body potassium but there is
paradoxical serum hyperkalaemia due to acidosis and
insulin deficiency.
26. Causes of DKA
May be the initial presentation of a newly diagnosed
case in 25% of cases of type 1 DM.
Most cases are usually precipitated by infection
May be a result of poor compliance to insulin.
May occur during adolescent changes eg menarche
Failure of insulin pumps and poor caregiver
competence
27. Clinicals
Altered mental status without evidence of head trauma
Tachycardia
Tachypnea or hyperventilation (Kussmaul respirations)
Normal or low blood pressure
Increased capillary refill time
Poor perfusion
Lethargy and weakness
Fever
Acetone odour of the breath reflecting metabolic acidosis
28. Lab work-up
Blood sugar confirms hyperglycemia
Urinalysis shows glycosuria and ketonuria
Serum potassium is very important
Arterial blood gases to establish acidosis
Renal function tests,
Hemogram, septic screen and HbA1c useful to
determine underlying cause
29. Treatment of DKA
Initial: ensure ABCs with securing airway and put on
oxygen, NPO and initiate empiric antibiotics.
1st hour: isotonic saline at 20ml/kg and lab work-up to
confirm DKA.
2nd hour and succeeding hours the goals are to slowly
reduce blood sugar, correct ketosis and acidosis and
continued restoration of fluid volume
30. Treatment (fluid and electrolyte
replacement)
As pointed out initial fluid of saline in 1st hr at 20ml/kg
which may be repeated if necessary.
Next 4-6 hrs IVF ringers or saline of the deficit
If one knows weight of pt replace deficit if not
assume 10% deficit.
Subsequently deficit is replaced by 0.45%- 0.9% saline
with potassium supplementation and the aim is to
replace this over 48hrs (usually 1.5-2x daily
maintenance)
31. Treatment (insulin therapy)
Start insulin therapy after 1st hour. This is to avoid
cerebral edema
Infuse insulin at 0.1U/kg/hr (boluses risk cerebral
edema)
Continue this infusion up to resolution of DKA (i.e.
pH> 7.3 and serum bicarb >15mmol/l )
Only add 5% dextrose when blood sugar <17mmol/l)
32. Insulin therapy
If sugar falling too fast (> 5mmol/l/hr) you may use
consider starting D5 earlier
In case of hypoglycaemia use D10 or D12.5 but DO
NOT stop insulin infusion till DKA corrected.
If patient to sensitive to insulin infuse at 0.05U/kg/hr
as long as acidosis is correcting.
33. Potassium therapy
At admission serum K+ levels may be normal or high
BUT there is total body K+ depletion.
Furthermore as treatment progresses K+ will reduce
due to insulin therapy and reducing H+
So replace K+ regardless
If hypoK+ at initial diagnosis start K+ at 20mmol/L
with initial fluid bolus.
If not start replacement at same time as insulin at 40
mmol/l
34. Potassium therapy
If hyperK+ defer supplementation till urine output
documented.
Subsequently monitor serum K+ and adjust
However K+ continues throughout IV infusion
Maximum infusion of K+ is 0.5 mmol/kg/hr and if
hypokalaemia persists inspite of this consider
reducing insulin infusion rate.
35. Acidosis
Isotonic fluid infusion usually corrects acidosis.
Bicarbonate usually not needed and may be harmful.
If severe acidosis ie pH < 6.9 and with cardiac
contractility compromised then cautiously give
bicarbonate at 1-2 mm0l/ kg over 1 hr
36. DKA mortality
Most deaths due to cerebral edema (80-90%)
Cerebral edema can occur before treatment but
usually occurs 1-2 days after treatment.
Close monitoring required to monitor for edema by
close neurological monitoring, meticulous fluid
therapy and input/output monitoring
37. Edema treatment
Initiate treatment as soon as the condition is
suspected.
Give mannitol 0.25-1 gram/kg IV over 20 minutes and
repeat if there is no initial response in 30 minutes to 2
hours (C,E)
Reduce the rate of fluid administration by 50%.
Hypertonic saline (3%), 5-10 mL/kg over 30 minutes,
may be an alternative to mannitol, especially if there is
no initial response to 1 g/kg mannitol (C).
38. Mannitol or hypertonic saline should be available at
the bedside
Elevate the head of the bed
Intubation and ventilation may be needed
Do brain imaging rule out other neurological
diseases
