Ppt about type 1 diabetes in children

1. Diabetes Mellitus in
Children
DM Type I
Made by:AHMED MOHD AKEEL
LA1-192(1)

2. Diabetes Mellitus in Children

3. Diabetes Mellitus
DM is a syndrome of disturbed
energy metabolism caused by
deficiency of Ins secretion or Ins
action at the cellular level that
results in altered fuel homeostasis
affecting carbohydrate, protein,
and fat.

4. World Statistics
246.000.000 patients with DM in the
World were reiterated at 2006 yr
380.000.000 – prognosis for 2025 yr
Every 10 seconds one patient
die from DM

5. World Statistics
Every years the DM type I
occurs in 70 000 children
EURODIAB: every year
increasing DM type I in adults
in 3% and in 4.8% in children

6. (на 1000 населения)
0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
1
9
9
1
1
9
9
2
1
9
9
3
1
9
9
4
1
9
9
5
1
9
9
6
1
9
9
7
1
9
9
8
1
9
9
9
2
0
0
0
2
0
0
1
2
0
0
2
2
0
0
3
2
0
0
4

7. Mortality from DM type I
Mortality DM type I
Mortality DM type I (1922
(1922-
-1972)
1972)
from 90% to 50%
from 90% to 50%
1922 г.
1922 г.
1 9 2 2 г .
1972 г.
1972 г.
1 9 7 2 г .
Green A. // Diabetologia. – 1985., 28: 3
Green A. // Diabetologia.
Green A. // Diabetologia. –
– 1985., 28: 33
1985., 28: 33
Снизилась на 40%
Снизилась
С н и з и л а с ь на 40%
н а 4 0 %
Decrease on the 40%

8. Historical Data
 Increasing of the urination was described
1500 yrs B.C. at Egypt
 Fist clinical description of the DM by Cels
(30-50 yrs Anno Domini)
 The term “Diabayo” – passing through
(30-90 yrs Anno Domini)
 1600 yr – the term “mellitus” (lat)- honey
due to sweet urine taste

9. Historical Data (c’d)
 1674 yr Tomas Willis (Oxford) supposed
that the sugar pass to urine from blood
 1841-1848 yrs Trommer and Felling –
methodic of the definition of blood sugar
by Copper Oxide
 1796 Rallo at first proposed to restrict the
carbohydrate intake to patients with DM

10. Historical Data (c’d)
 1813-1878 yrs Klod Bernar
discribed the pathogenesis of
hyperglycemia
 1869 yr medical student Paul
Langerhans discovered the cells
congestion in pancreas
 1874 yr Kussmaul discovered ketons,
aceton, described specific type of
breathing

11. Historical Data (c’d)
 1989 yr Mering & Minkovsky established
that the dogs with pancrectomy develops
hyperglycemia and further death
 1902 yr Opy – described the degeneration
of the Langergans islet
 1907 yr Lane Bersley (Chicago) discovered
pancreatic cells type A and type B

12. Historical Data (c’d)
 1955 yr Sanger
(Cambridge) –
discovery aminoacid
structure in
molecular of Ins

13. С-peptide is the predecessor of Ins
1969 yr Steiner – invented biosynthesis of
the C-peptide

14. 1973 yr mono component - Ins was
synthesized

15. Etiologic classification of DM
I. Type I DM (β-cell destruction,
usually leading to absolute Ins
deficiency)
II. Type II DM (may rang from
predominantly Ins resistance with
relative Ins deficiency to a
predominantly receptor defect with
Ins resistance)

16. Etiologic classification of DM (c’d)
III. Other specific types
A. Monogenic DM
B. Exocrine pathology of pancreas
C. Endocrine diseases
D. Drugs
E. Genetics syndromes such as Down,
Turner etc.

17. The onset DM
type I occurs
predominantly
in childhood,
with median age
of 7 to 15 yrs,
but it may
present at any
age

18. DM type I
DM type I is
characterized by
autoimmune
destruction of
pancreatic β-
cells

19. DM type I
Β-cells
destruction may
be due to drugs,
viruses,
mitochondrial
defects, ionizing
radiation, etc

20. DM (DM I type)
Genetic susceptibility to type I DM is
controlled by alleles of the major
hystocompatability complex class II
genes expressing human leukocyte
antigens (HLA) that associated with
antibodies to glutamatic acid
decarboxylase
DM I type is associated with other
autoimmune diseases such as
thyroiditis, Celiac disease, multiply
sclerosis, Addison disease, and etc.

22. Manifestation of the DM if the 80-
90% betta cells were destructed

23. DM II type –resistant to Ins

24. Etiologic classification of DM (c’d)
III. Other specific types
 Genetic defects of β-cell function
chromosome 12, HNF-1ά - MODY-3
chromosome 7, glucokinase, MODY-2
chromosome 20, HNF-4ά - MODY-1
Mitochondrial DNA
MODY- maturity-onset diabetes of the
young *HNF –hepatocyte nuclear
factor gene mutation

25. Etiologic classification of DM (c’d)
III. Other specific types
 Genetic defects in Ins
action
Type A Ins resistance
Leprechaunism
Rabson-Mendenhall syndrome
Lipoatropic diabetes
(Lorens syndrome)

26. Type A
 Adolescence
 Ins-resistance in absence of obesity
 Acanthosis Nigricans
 Androgen Excess & Hypertrichosis
 Gene involved Insulin receptor
 Recessive

27. Leprechaunism
 Congenital
 Abnormal faces
 Large genitalia
 SGA and growth retardation
 Rarely survive infancy
 Acanthosis Nigricans
 Gene involved Insulin receptor & GH-
resistence
 Recessive

28. Leprechaunism

29. Rabson-Mendenhall
 Congenital
 Extreme Growth retardation
 Abnormal dentition
 Acanthosis Nigricans
 Androgen Excess & Hypertrichosis
 Gene involved Insulin receptor
 Recessive

30. Lipodystrophy
Lorens syndrome
 Congenital or Adolescence
 Loss of subcutaneous fat – partial or total
 Acanthosis Nigricans
 Androgen Excess & Hypertrichosis
 Gene involved Total: Seipin & AGPAT2
(recessive) Partial :Lamin AC & PPARG
(dominant)

31.  The key feature of all insulin resistance
syndromes are acanthosis nigricans,
androgen excess and massively raised
insulin concentrations in the absence of
obesity

32. Maternal transmission of mutated or deleted
mitochondrial DNA (mtDNA) and the
mitochondrial tRNA (leu(UUR)) gene (B) can
result in maternally inherited diabetes.
MELAS syndrome:
 mitochondrial myopathy
 Encephalopathy
 lactic acidosis
 stroke-like syndrome
Mitochondrial diabetes is commonly associated
with sensorineural deafness and short stature.
The diabetes is characterised by progressive
non-autoimmune beta-cell failure and may
progress to needing insulin treatment rapidly.

33. Etiologic classification of DM (c’d)
III. Other specific types
 Diseases of the exocrine pancreas
Pancreatitis
Trauma, pancreatomy
Neoplasia
Cystic fibrosis
Hemochromatosis
Fibrocalculous pancreatopathy
Pancreatic resection

34. Etiologic classification of DM (c’d)
III. Other specific types
 Endocrinopathies
Acromegaly
Cushing disease
Glucagonoma
Pheochromocytoma
Hyperthyroidism
Somatostatinoma
Aldosteronoma

35. Etiologic classification of DM (c’d)
III. Other specific types
 Infections
Congenital rubella
Cytomegalovirus
Hemolitic-uremic
syndrome
→→→

36. Etiologic classification of DM (c’d)
III. Other specific types
 Genetic syndromes
Down syndrome
Klinefelter syndrome
Wolfram syndrome
Friedreich ataxia
Huntington chorea
Laurence-Moon & Bardet-
Biedl syndrome
Myotonic distrophy
Porphyria
Prader-Willi syndrome

37. Wolfram syndrome (DIDMOAD)
DI-diabetes insipidus
DM-diabetes mellitus
OA-optical atrophy
D- deafness

38. ????

39. Prader-Willi syndrome

40. Etiologic classification of DM (c’d)
III. Other specific types
 Gestational DM
 Neonatal DM

41. Neonatal diabetes
 There is good evidence that diabetes
diagnosed in the first 6 months is not
Type I DM as neither autoantibodies nor
an excess of high Type I HLA susceptibility
are found in these patients.
 Neonatal diabetes is insulin requiring
diabetes which is usually diagnosed in the
first three months of life.

42. Neonatal diabetes
Clinically two subgroups
were recognized:
transient neonatal
diabetes mellitus
(TNDM) & permanent
neonatal diabetes
mellitus (PNDM)

43. Transient neonatal diabetes
 anomalies on 6q24 locus
 DM associated within the first week and resolves
around 12 weeks
 50% of cases DM will reoccur during the paediatric
age range
 Macroglossia seen in 23%
 Initial glucose values can be very high (range12-57
mmol/L) and so insulin is used initially although the
dose can rapidly be reduced.
 The response to oral treatment such as
sulphonylureas or metformin is uncertain

44. Permanent neonatal diabetes
 Kir6.2 mutations
 Only 10% have a remitting form of DM that may
latter relapse
 Most patients have isolated DM
 20% have developmental delay of motor and
social function & generalized epilepsy so called
DEND syndrome Developmental delay, Epilepsy
and Neonatal Diabetes
 Patients have all the clinical features of insulin
dependency do not have detectable C peptide.
It has been shown that these patients can not
be successfully treated with oral sulphonylureas.

45. Etiologic classification of DM (c’d)
III. Other specific types
 Drug- or chemical-induced
Pentamidine, Nicotinic acid
Glucocorticoids
Thyroid hormone
ß-adrenergic agonists
Thiasides
Β-Interferon & others

46. Insulin
 Ins is synthesized on the ribosoms of
pancreatic islet beta cells and is released
into the circulation as a molecule
comprised of two separate straight
polypeptide chains linked by disulfide
bridges between and within these chains

47. Ins is the major anabolic hormone
of the body
Ins action is on
target cells in
tissues such as
liver, adipocytes
and muscle

49. Metabolic events during the fed
and fasted states (liver)
High-Ins (fed) & Low Ins (fasted)state
Glucose uptake Glucose production
Glycogen synthesis Glycogenolysis
Absent gluconeogenesis Present G-sis
Lipogenesis Absent l-sis
Absent ketogenesis Ketogenesis

50. Metabolic events during the fed
and fasted states (muscle)
High-Ins (fed) & Low Ins (fasted)state
Glucose uptake Absent glucose uptake
Glucose oxidation Fatty acid άketooxydation
Glycogen synthesis Glycogenolysis
Protein syntesis Proteolysis and amino
acid release

51. Metabolic events during the fed
and fasted states (Adipose tissue)
High-Ins (fed) & Low Ins (fasted)state
Glucose uptake Absent Glucose uptake
Lipid synthesis Lipolysis and fatty acid
release
Triglyceride uptake Absent triglyceride
uptake

52. Pathophysiology of DM type I
 Progressive destruction of β-cells leads to
progressively more severe Ins deficiency
with involving classical stress hormones
(epinephrine, cortisol, growth hormone,
and glucagon) so called counter-
regulatory hormones

53. Ins deficiency, acting in concert
with the excessive concentration
of epinephrine, cortisol, growth
hormone, and glucagon will result
in unrestrained glucose
production while glucose
utilization is impaired, so that
hyperglycemia develops.

54. Ins deficiency and elevating
counter-regulatory hormones
leads to lipolysis and impaired
lipid synthesis and elevation in
plasma total lipids, cholesterol,
triglycerids, and free fatty acids.

56. The hormonal interplay of Ins
deficiency and glucagon excess
shunts the free fatty acids to
ketone body formation
Acetone
Acetoacetate
Β-oxyoil acid

57.  Accumulation of ketoacids results in
metabolic acidosis and the compensatory
rapid deep breathing, which is an attempt
to excrete excess CO2 (Kussmaul’s
respiration)
 Acetone, formed by nonenzymatic
conversation of acetoacetate, is
responsible for the characteristic fruity
odor of the breath

58.  Ketones are readily excreted in the urine
in association with cations, further
compounding losses of water and
electrolytes (dehydration)
 With progressive dehydration, acidosis,
hyperosmolality, and diminished cerebral
oxygen utilization, consciousness becomes
imparired and ultimately results in coma.

60. DM
 The loss of weight is on the basis of the
catabolic state and urinary losses of
calories due to polyuria
 The no effective calories balance lead to
the hunger & polyphagia (despite the
increase food intake calories cannot be
utilized) & weight loss occurs

63. DM
 Glucosuria results when the renal
threshold of ≈ 160 ml/dl (> 8.88 mmol/L)
is exceeded; the resultant osmotic diuresis
produces polyuria, dehydration, an
increase in osmolality, and compensatory
polydipsia

64. DM
 Pyogenic skin infection are most
uncommon as a presenting complaint,
although vaginitis in teenage girls may be
the presenting feature

65. Clinical presentation
About 30% of patients initially present with
frank diabetic ketoacidosis:
Air hunger
Kussmaul’s respiration
Acetone on the breath
Obtundation of consciousness or coma
Vomiting
Dehydration

66. Hyperglycemia

67. Hyperglycemia

68. Clinical presentation
 Polyuria
 Polydipsia
 Polyphagia
 Weight loss
 Lethargy
 weakness
These symptoms may be present for days to
weeks

69. Particularities DM in infants
 Lability of the water &
mineral metabolism
 Stopping or loss body
weight
 Appetite increase or
normal
 Thirst, active sucking

70. Particularities DM in infants
 Starch napkins or sticky
stains due to glucosuria
 Dry skin, ↓ turgor, skin
infection

71. 2 types of DM manifestation in
infants
 First – acute onset, severe dehydration,
intoxication, vomiting, coma as a toxico-
infection shock
 Second – dystrophy develops gradually,
infection diseases connect
 Ketonuria is absent to 4 mo old due to
liver immaturity

72. Diagnosis of DM N.B!
 Clinical presentation & paraclinic: hyperglicemia,
glucosuria, ketonuria
Additional:
 ↓ or absents of C-peptide
 ↑ glicolized Hb (HbAic)
 ↑ fructosamine
 presents of the antibodies to ß cells, Ins
and to differens glutamatdecarboxilase
isoformes

73. Criteria of DM compensation
 The aim of treatment –”QULITY OF LIFE”
 The adequate growth & development of
child
 Active social position in life & society
 Decreasing acute complication and
prolong late complications of DM
 Normal life duration

74. Criteria of DM compensation (c’d)
in childhood
 Glucose level fasting 4-8 mmol/L
 Glucose after feeding 10-11mmol/L (3.3-
8.3 mmol/L – less than renal threshold)
 Night Glucose level 6-8 mmol/L
 Episodes of Hypoglycemia are absent
 Glucose absent in urine

75. Criteria of DM compensation (c’d)
 Normal lipid, protein and mineral
metabolism
 HbAic, % - 5-7
 Cholesterol mmol/L -< 5.2
 Triglicerids mmol/L - < 1.7

76. Differential Diagnosis
 Diabetes Insipidus
 Appendicitis
 Fancony syndrome
 Diabetes Mellitus type II

77. Factors influencing
vasopressing secretion
INCREASED SECRETION
 Hypovolemia
 Hyperosmolality
 Upright position
 Central hyperthermia
 Stress and anxiety
 Cerebral disease
 Chest disease
 Malignancies
 Drugs (Carbamazepine, clofibrate Nicotine, angiotensin
II Cholinergic drugs, Morphine, barbiturates)

78. Factors influencing
vasopressing secretion
DECREASED SECRETION
 Hypervolemia
 Hyperosmolality
 Recumbent position
 Central hyperthermia
 Diabetes insipidus
 Drugs & Alcohol (Dilantin, Anticholinergic
agents)

79. POLYURIC CONDITIONS
MIMICKING VASOPRESSIN
DEFICIENCY
 Physiologic suppression of vasopressin
secretion
 Psychogenic polydipsia
 Organic polydipsia (hypothalamic disease)
 Drug induced polydipsia (thioridazine,
tricyclics)

80. POLYURIC CONDITIONS
MIMICKING VASOPRESSIN
DEFICIENCY
 Reduced renal responsiveness to vasopressin
 Genetic: nephrogenic diabetes insipidus medullary cystic
disease
 Pharmacologic: lithium, demeclocycline, penthrane,
diuretics
 Osmotic diuresis: diabetes mellitus reduced nephron
population
 Electrolyte disturbance: hypercalcemia hypokalemia
 Renal disease:postobstructive diuresis, renal tubular
acidosis pyelonephritis, papillary necrosis, sickle cell
disease
 Hemodynamic: hyperthyroidism

81. Diabetic ketoacidosis
 Hyperglycemia
 Ketonemia
 Acidosis (pH≤7.3 & bicarbonate less than
15 mEq/L)
 Glucosuria
 Ketonuria

82. Complications of DM (acute)
 Ketoacidosis, ketoacidotic coma
 Dehydration
 Nonketotic hyperosmolar coma
 Hypoglicemia, hypoglicemic coma
 Lactoacidotic coma

83. Complications of DM
 Somogy phenomenon
 Dawn phenomenon
 Brittle Diabetes

84. Complications of DM (long-term)
 Diabetic retinopathy
 Diabetic nephropathy
 Angiophathy of lower
extremities
 Diabetic neuropathy
(periferal, central,
autonomic)

85. Complications of DM (long-term)
 Mauriac syndrome, Nobecur syndrome
 Syndrome of limited joint mobility
(hairopathy)
 Skin pathology (lipoid necrobiosis,
lipodystrophy, paronichia and etc)

86. lipoid necrosis's

87. lipoid necrobiosis

88. lipoid necrobiosis