2. DIABETES MELLITUS (DM)
Is a common, chronic, metabolic syndrome characterized
by hyperglycemia as a cardinal biochemical feature.
The major forms of diabetes are classified according to
those caused by deficiency of insulin secretion due to
pancreatic β-cell damage (type 1 DM, or T1DM) and
those that are a consequence of insulin resistance
occurring at the level of skeletal muscle, liver, and adipose
tissue, with various degrees of β-cell impairment (type 2
DM, or T2DM).
3. ETIOLOGIC CLASSIFICATIONS OF
DM
Type I diabetes (β-cell destruction, usually leading to absolute
insulin deficiency) Immune mediated , Idiopathic
Type 2 diabetes (may range from predominantly insulin
resistance with relative insulin deficiency to a predominantly
secretory defect with insulin resistance)
Other specific types
- Genetic defects of β-cell function (MODY 1-6)
- Genetic Defects in insulin action
-Pancreatitis, Drug-or chemical-induced, Trauma,
pancreatectomy
4. DIABETES MELLITUS
Infections
Congenital rubella, coxackie virus
Cytomegalovirus
Other genetic syndromes associated with
diabetes
Down syndrome
Klinefelter syndrome
Turner syndrome
prader will syndrome
5. DIABETES MELLITUS
Gestational diabetes mellitus
Neonatal diabetes mellitus
Transient—without recurrence
Transient—recurrence 7–20 yr later
Permanent from onset
6. THE NATURAL HISTORY
INCLUDES 4 DISTINCT STAGES:
1. preclinical β-cell autoimmunity with progressive
defect of insulin secretion,
2. onset of clinical diabetes,
3. transient remission “honeymoon period,” and
4.established diabetes associated with acute and
chronic complications and decreased life
expectancy.
7. IMPAIRED GLUCOSE TOLERANCE.
The term impaired glucose tolerance (IGT) refers to a
metabolic stage that is intermediate between normal
glucose homeostasis and diabetes.
A fasting glucose concentration of 99 mg/dL is the
upper limit of “normal.”
This choice is near the level above which acute-phase
insulin secretion is lost in response to IV
administration of glucose and is associated with a
progressively greater risk of the development of
microvascular and macrovascular complications.
8. PATHOGENESIS
The autoimmune attack on the pancreatic islets leads
to a gradual and progressive destruction of β cells,
with loss of insulin secretion.
It is estimated that, at the onset of clinical diabetes,
80–90% of the pancreatic islets are destroyed.
9. PATHOGENESIS
Regeneration of new islets has been detected at onset
of T1DM, and it is thought to be responsible for the
honeymoon phase (a transient decrease in insulin
requirement associated with improved β-cell
function).
10. PATHOPHYSIOLOGY
Insulin is our most important anabolic hormone!
Saving , storing and up building of carbohydrate , protein
and fat.
Carbohydrate -Insulin stimulates the insulin receptor on
the cell surface Glut 4 , a glucose transporter, is sent to the
cell surface of the muscle to pick up glucose by endocytosis.
The more insulin the more transporter!!
Glucose is phosphorylated and ready for either storing as
glycogen or glycolysis and energy production (ATP)
11. PATHOPHYSIOLOGY
Fat -Insulin preservs the fat stores (It antagonizes
the adrenaline sensitive lipase in fat tissue)
Protein -Aminoacid uptake in the cells is stimulated
and breakdown of protein is reduced.
12. PATHOPHYSIOLOGY.
Insulin levels must be lowered to then mobilize stored
energy during the fasted state.
Thus, in normal metabolism, there are regular
swings between the postprandial, high-insulin
anabolic state and the fasted, low-insulin
catabolic state that affect liver, muscle, and adipose
tissue .
13. PATHOPHYSIOLOGY.
T1DM is a progressive low-insulin catabolic state in which
feeding does not reverse but rather exaggerates these
catabolic processes.
With moderate insulinopenia, glucose utilization by muscle
and fat decreases and postprandial hyperglycemia appears
At even lower insulin levels, the liver produces excessive
glucose via glycogenolysis and gluconeogenesis, and fasting
hyperglycemia begins.
Postprandial hyperglycemia then fasting
hyperglycemia will occur
14. PATHOPHYSIOLOGY.
Hyperglycemia produces an osmotic diuresis
(glycosuria) when the renal threshold is exceeded (180
mg/dL; 10 mmol/L).
The resulting loss of calories and electrolytes, as well
as the persistent dehydration, produce a physiologic
stress with hypersecretion of stress hormones
(epinephrine, cortisol, growth hormone, and glucagon).
15. These hormones, in turn, contribute to the metabolic
decompensation by further impairing insulin secretion
(epinephrine),
by antagonizing its action (epinephrine, cortisol, growth
hormone), a
by promoting glycogenolysis, gluconeogenesis, lipolysis, and
ketogenesis (glucagon, epinephrine, growth hormone, and
cortisol)
Impairing insulin secretion , antagonizing insulin action ,
decrease glucose utilization , increase glucosneogenesis
and ketogenesis
17. CLINICAL PRESENTATION
Childhood type 1 diabetes can present in several different ways.
Classic new onset
Diabetic ketoacidosis
Silent (asymptomatic) incidental discovery
Classic new onset - Hyperglycemia without acidosis is the
most common presentation of childhood type 1 diabetes.
Symptoms are caused by hyperglycemia and include polyuria,
polydipsia, weight loss despite increased appetite initially
(polyphagia), and lethargy.
18. DIABETIC KETOACIDOSIS
As an initial presentation or in a known case of DM
when they omit their insulin or when there is
infection or stress.
Can be classified as mild,moderate and severe DKA
Normal Mild Moderate Severe
CO 2
meq/l(venous
)
20-28 16-20 10-15 <10
PH(venous) 7.35-7.45 7.25-7.35 7.15-7.25 <7.15
Clinical No change Alert but
fatigued
Kussmal
breathing
,sleepy
comatous
19. DIABETIC KETOACIDOSIS
When extremely low insulin levels are reached, keto
acids accumulate. Keto acids produce abdominal
discomfort, nausea, and emesis.
Dehydration accelerates, causing weakness and
polyuria persists. As in any hyperosmotic state, the
degree of dehydration may be clinically
underestimated
Ketoacidosis exacerbates prior symptoms and leads to
Kussmaul respirations (deep, heavy, rapid breathing),
fruity breath odor (acetone), diminished
neurocognitive function, and possible coma.
20. DIAGNOSIS
Fasting plasma glucose ≥ 126 mg/dL (7 mmol/L)
on two occasions Symptoms of hyperglycemia and
a random venous plasma glucose ≥ 200 mg/dL
(11.1 mmol/L)
Abnormal oral glucose tolerance test (OGTT)
defined as a plasma glucose ≥ 200 mg/dL (11.1
mmol/L) measured two hours after a glucose load
of 1.75 g/kg (maximum dose of 75 g)
Most children and adolescents are symptomatic
and have plasma glucose concentrations well
above ≥ 200 mg/dL (11.1 mmol/L); thus, OGTT is
seldom necessary to diagnose type 1 diabetes.
21. CHALLENGES IN PEDIATRICS DM
There are unique challenges in caring for children
and adolescents with diabetes that differentiate
pediatric from adult care.
These include the obvious differences in the size of
the patients, developmental issues such as the
unpredictability of a toddler's dietary intake and
activity level, and medical issues such as the
increased risk of hypoglycemia and diabetic
ketoacidosis.
Because of these considerations, the management
of a child with type 1 diabetes must take into
account the age and developmental maturity of the
child.
22. GOALS
Successful management of children with
diabetes includes the following :
Balancing strict glycemic control, which
reduces the risk of long-term sequelae, and
avoidance of severe hypoglycemia, which is
more likely with stricter control.
In children, targeted glycemic goals define
what is thought to be the best balance between
these long- and short-term complications.
23. GOALS
Maintaining normal growth, development, and
emotional maturation.
Increasing self-independent management as the child
grows is an ongoing goal.
Training the patient and family to provide appropriate
daily diabetes care in order to attain glucose control
within the range of predetermined goals, and to
recognize and treat hypoglycemia.
24. DKA MANAGEMENT
1.Volume expansion
10-20 ml/kg R/L or N/S over 1 hour
2.Insulin therapy and K+ replacement
- 0.1u /kg/hr continuous insulin mxt
-0.5 u/kg/ every 4-6 hourly intermittent insulin mxt
-K + 20-40 meq/L of fluid
3. Fluid mxt 85 ml/kg + maintenance fluid –bolus/23
hrs(0.45 % N/S and when glucose is < 250 mg/dl
change the fluid to 5 % D/W
25. DKA MXT RISKS
Hypoglycemia
Cerebral edema
Hypokalemia
So we need to follow the child with V/S, frequent
glucose and electrolyte measurement to act
accordingly.
Bed side mannitol 1gm/kg is important
26. Treatment
Insulin Therapy.
Children with long-standing diabetes and no insulin
reserve require about 0.7 U/kg/d if prepubertal, 1.0
U/kg/d at midpuberty, and 1.2 U/kg/d by the end of
puberty
Basic education – about the insulin injection , meal
planning ,exercise, about symptoms of
hypo/hyperglycemia and importance of SMBG and the
impact of poor control of DM.
27. EXERCISE
No form of exercise, including competitive sports,
should be forbidden to the diabetic child.
But the risk of hypoglycemia is there during or
within hours after exercise so BG measurement
is important .
They have to take candy or carbonated juice to
take immediately if there are symptoms of
hypoglycemia
29. T2DM MANAGEMENT
Weight loss and physical exercise are said to be
the main strategies in controlling glucose level in
T2DM patients
Oral hypoglycemic agents like metiformin can be
tried
Insulin if they have ketonuria
30. Long term complications of DM
-Micro vascular
complications( Retinopathy,
nephropathy)
-Macro vascular complication
-Growth failure and delayed puberty
