Diabetes Mellitus PPT

Diabetes Mellitus Pediatrics

1. UPDATE ON UPDATE ON
CHILDHOOD CHILDHOOD
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 b-cell
destruction)
Type 2 Diabetes
(defects in insulin secretion or
action)
Other specific types

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 b-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 b-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 (b-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 b-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 b-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 action Long 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
control.

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