Diabetes Mellitus Pediatrics

1. UPDATE ONUPDATE ON
CHILDHOODCHILDHOOD
DIABETES MELLITUSDIABETES MELLITUS
Abdelaziz Elamin
MD, PhD, FRCPCH
Professor of Child
Health
Sultan Qaboos
University

2. DEFINITION
 The term diabetes mellitus describes
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.

3. 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; in
Oman it is estimated as 4/100000 per
year.

4. OLD CLASSIFICATION
(1985)
 Type 1, Insulin-dependent (IDDM)
 Type 2, Non Insulin-dependent
(NIDDM)
– obese
– non-obese
– MODY
 IGT
 Gestational Diabetes

5. WHO CLASSIFICATION
2000
 Is based on etiology not on type
of treatment or age of the
patient.
 Type 1 Diabetes
(idiopathic or autoimmune β-cell
destruction)
 Type 2 Diabetes
(defects in insulin secretion or
action)

6. WHO
CLASSIFICATION/2
 Both type 1 & type 2 can be further
subdivided into:
Not insulin requiring
Insulin requiring for control
Insulin 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.

7. DIAGNOSTIC CRITERIA
 Fasting blood
glucose level
 Diabetic
 Plasma >7.0 mmol
 Capillary >6.0
mmol
 IGT
 Plasma 6.0-6.9 mmol
 Capillary 5.6-6.0
mmol
 2 hours after
glucose load
(Plasma or capillary
BS)
 IGT
 7.8-11.0
 Diabetic level
 > 11.1 (200 mg)

8. 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 diabetes
 Transient neonatal diabetes
 Maturity-onset diabetes of the young
 Secondary diabetes e.g. in cystic
fibrosis or Cushing syndrome.

9. MODY
 Usually affects older children &
adolescents
 Not rare as previously
considered
 5 subclasses are identified, one
subclass has specific mode of
inheritance (AD)
 Not associated with immunologic
or genetic markers
 Insulin resistance is present

10. TRANSIENT NEONATAL
DIABETES
 Observed in both term & preterm
babies, but more common in preterm
 Caused by immaturity of islet β-cells
 Polyuria & dehydration are prominent,
but baby looks well & suck vigorously
 Highly sensitive to insulin
 Disappears in 4-6 weeks

11. 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.

12. TYPE 1 DIABETES:
ETIOLOGY
 Type 1 diabetes mellitus is an
autoimmune disease.
 It is triggered by
environmental factors in
genetically susceptible
individuals.
 Both humoral & cell-mediated
immunity are stimulated.

13. GENETIC FACTORS
Evidence of genetics is shown in
Ethnic differences
Familial clustering
High concordance rate in twins
Specific genetic markers
Higher incidence with genetic
syndromes or chromosomal
defects

14. AUTOIMMUNITY
 Circulating antibodies against β-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.

15. ENVIRONMENTAL
INFLUENCE
 Seasonal & 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.

16. ENVIRONMENTAL
SUSPECTS
 Viruses
Coxaschie B
Mumps
Rubella
Reoviruses
 Nutrition & dietary factors
Cow’s milk protein
Contaminated sea food

17. OTHER MODIFYING
FACTORS
 The counter-regulatory
hormones:
glucagon
cortisol,
catecholamines
thyroxin,
GH & somatostatin
sex hormones
 Emotional stress

18. ETIOLOGIC MODEL
 The etiologic model of type 1
diabetes resembles that of
Rheumatic fever.
 Rheumatic fever was prevented by
elimination of the triggering
environ. factor (β-streptococci).
 Similarly type 1 diabetes may be
prevented by controlling the
triggering factors in high risk
persons.

19. CLINICAL
PRESENTATIONS
Classical symptom triad:
polyuria, polydipsia and weight
loss
DKA
Accidental diagnosis
Anorexia nervosa like illness

20. DIAGNOSIS
 In symptomatic children a
random plasma glucose >11
mmol (200 mg) is
diagnostic.
 A modified OGTT (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.

21. NATURAL HISTORY
 Diagnosis & initiation of
insulin
 Period of metabolic recovery
 Honeymoon phase
 State of total insulin
dependency

22. 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 of
glycogen & metabolic re-balance.

23. HONEYMOON PERIOD
 Due to β-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.

24. COMPLICATIONS OF
DIABETES
 Acute:
DKA
Hypoglycemia
 Late-onset:
Retinopathy
Neuropathy
Nephropathy
Ischemic heart disease &
stroke

25. TREATMENT GOALS
 Prevent death & alleviate symptoms
 Achieve biochemical control
 Maintain growth & development
 Prevent acute complications
 Prevent or delay late-onset
complications

26. TREATMENT
ELEMENTS
 Education
 Insulin therapy
 Diet and meal planning
 Monitoring
HbA1c every 2-months
Home regular BG monitoring
Home urine ketones tests when
indicated

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

28. INSULIN
 A polypeptide made of 2 β-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.

29. 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.

30. TYPES OF INSULIN
 Short acting (neutral, soluble,Short acting (neutral, soluble,
regular)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

31. 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.

32. INSULIN REGIMENS
 Twice 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.

33. INSULIN ANALOGS
 Ultra short actingUltra short acting
 Insulin Lispro
 Insulin Aspart
 Long acting without peak actionLong acting without peak action
to simulate normal basal insulinto simulate normal basal insulin
 Glargine

34. NEW INSULIN
PREPARATIONS
 Inhaled 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.

35. ADVERSE EFFECTS OF
INSULIN
 Hypoglycemia
 Lipoatrophy
 Lipohypertrophy
 Obesity
 Insulin allergy
 Insulin antibodies
 Insulin induced edema

36. PRACTICAL
PROBLEMS
 Non-availability of insulin in poor
countries
 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

37. DIET REGULATION
 Regular meal plans with calorie
exchange options are encouraged.
 50-60% of required energy to be
obtained from complex
carbohydrates.
 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.

38. EXERCISE
 Decreases 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.

39. MONITORING
 Compliance (check records)
 HBG tests
 HbA1 every 2 months
 Insulin & meal plan
 Growth & development
 Well being & life style
 School & hobbies

40. ADVANCES IN
MONITORING
 Smaller & accurate meters for
intermittent BG monitoring
 Glucowatch continuous monitoring
using reverse iontophoresis to
measure interstitial fluid glucose
every 20 minutes
 Glucosensor that measures s/c
capillary BG every 5 minutes
 Implantable sensor with high & low
BG alarm

41. ADVANCES IN
MANAGEMENT
 Better understanding of diabetes
allows more rational approach to
therapy.
 Primary prevention could be
possible if the triggering factors
are identified.
 The DCCT studies proves beyond
doubt that chronic diabetic
complication can be controlled or
prevented by strict glycemic

42. TREATMENT MADE
EASY
 Insulin pens & new delivery
products
 Handy insulin pumps
 fine micro needles
 Simple accurate glucometers
 Free educational material
 computer programs for
comprehensive management &
monitoring

43. TELECARE SYSTEMS
 IT has improved diabetes care
 Internet sites for education &
support
 Web-based systems for telecare
are now available. The patient
feeds his HBGM data and get the
physician, nurse & dietician
advice on the required
modification to diet & insulin
treatment.

44. 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 (dawn
phenomenon) may go
unrecognized.

45. FUTURE PROMISES
 The 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.

46. Pancreas & Islet Cell
Transplantation
 Pancreas 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.

47. IMMUNE MODULATION
 Immunosuppressive therapy for
Newly diagnosed
Prolonged the honey moon
For high risk children
 Immune modulating drugs
Nicotinamide
mycophenolate

48. GENE THERAPY
 Blocks the immunologic attack
against islet-cells by DNA-
plasmids encoding self antigen.
 Gene encode cytokine inhibitors.
 Modifying gene expressed islet-
cell antigens like GAD.

49. PREDICTION OF
DIABETES
 Sensitive & specific immunologic
markers
GAD Antibodies
GLIMA antibodies
IA-2 antibodies
 Sensitive genetic markers
• HLA haplotypes
• DQ molecular markers

50. PREVENTION OF
DIABETES
Primary 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

51. Dreams are the seedlings
of realities