This document discusses childhood diabetes mellitus. It defines diabetes as a metabolic disorder characterized by chronic hyperglycemia. Type 1 diabetes accounts for over 90% of childhood cases and is an autoimmune disease triggered by environmental factors in genetically susceptible individuals. Proper treatment involves education, insulin therapy tailored to the individual, diet and exercise, and regular monitoring to prevent complications and achieve metabolic control goals. Advances allow more precise glucose monitoring and individualized insulin regimens.

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