2. INTRODUCTION
Chronic metabolic syndrome characterized by
hyperglycemia
Pathophysiology:
Absolute insulin deficiency OR
Absolute insulin resistance OR
Combination of defects in both
3. ETIOLOGICAL CLASSIFICATION: ADA 2014
I. Type 1 diabetes (beta cell destruction: Insulin deficiency)
1 . Immune mediated
2 . Idiopathic
II. Type 2 diabetes (variable combination of insulin resistance and
insulin deficiency)
1 . Typical
2 . Atypical
III. Other specific types
A. Genetic defects of beta cell function
1.Maturity onset diabetes of young(MODY)
2. Mitochondrial DNA mutation
3. Others
4. B. Genetic defects in insulin action
1. Type A insulin resistance
2. Leprechaunism (elfin features, insulin receptor defect, IUGR)
3. Rabson–Mendenhall syndrome
4. Lipoatrophic diabetes
5. Others
C. Diseases of the exocrine pancreas
Pancreatitis, Trauma/pancreatectomy, Neoplasia, Cystic fibrosis,
Hemochromatosis, Fibrocalculous pancreatopathy, etc
D. Endocrinopathies
1. Acromegaly 5. Hyperthyroidism
2. Cushing’s syndrome 6. Somatostatinoma
3. Glucagonoma 7. Aldosteronoma
4. Phaeochromocytoma 8. Others
5. E. Drug- or chemical-induced
1. Vacor 7. β-Adrenergic agonists
2. Pentamidine 8. Thiazides
3. Nicotinic acid 9. Dilantin
4. Glucocorticoids 10. α-Interferon
5. Thyroid hormone 11. Others
6. Diazoxide
F. Infections
1. Congenital rubella 3. Enterovirus
2. Cytomegalovirus 4. Others
G. Uncommon forms of immune-mediated diabetes
1. ‘Stiff-man’ syndrome 4. IPEX
2. 2. Anti-insulin receptor antibodies 5. Others
3. 3. Autoimmune polyendocrine syndrome (APS) types I and II.
6. H . Other genetic syndromes sometimes associated with diabetes
1. Down syndrome
2. Klinefelter syndrome
3. Turner syndrome
4. Wolfram syndrome
5. Friedreich’s ataxia
6. Huntington’s chorea
7. Laurence–Moon–Biedl syndrome
8. Myotonic dystrophy
9. Porphyria
10. Prader–Willi syndrome
11. Other
IV. Gestational diabetes mellitus (GDM)
7. LESS COMMON TYPES OF DIABETES IN CHILDREN
Type 2 DM
Screening:
Children: age ≤18 yrs
*BMI >85th percentile for age and sex, weight for height >85th percentile, or weight >120% ideal
for height
†Native American, African American, Latino, Asian American, Pacific Islander
‡Acanthosis nigricans, hypertension, dyslipidemia, PCOS, or small-for-gestational-age birth
weight §Sleep apnea, hepatic steatosis, orthopedic complications, psychosocial concerns
Consider for all children who are overweight* and have ≥2 of any of the following risk
factors:
• Family history of type 2 diabetes in first- or second-degree relative
• Race/ethnicity†
• Signs of insulin resistance or conditions associated with insulin resistance‡
• Maternal history of diabetes or GDM during child’s gestation
8. TYPE 2 DM CONTD...
Begin testing at age 10 yrs or onset of puberty
Test every 3 yrs
A1C test recommended for diagnosis in children and
adolescents
At Diagnosis After Diagnosis
• Perform eye exam
• Measure risk factors
o Blood pressure
o Fasting lipids
o Albumin excretion
Similar screening, treatment as for
type 1 diabetes for
• Hypertension
• Albumin excretion
• Dyslipidemia
• Retinopathy
9. LESS COMMON TYPES OF DIABETES IN CHILDREN CONTD...
Monogenic diabetes
o Originally termed MODY
o Mild , non-ketotic diabetes
o Onset: 9-25 yrs
o AD inheritance
o Mutation in genes for development /function of beta cells
o Strict criteria for diagnosis:
o At least 3 generations affected with AD transmission
o At least 1 affected subject diagnosed < 25 yrs
10. LESS COMMON TYPES OF DIABETES IN CHILDREN CONTD...
Neonatal diabetes
o Rare (1 in 100 000-400 000 births)
o 1st six months of life
o May present as late as 9-12mnth
o Alternative term: monogenic diabetes of infancy
o Permanent:
o 50% cases
o Lifelong treatment
o Transient:
o Remits within weeks or months
o 50-60%-permanent diabetes, typically around puberty
o Chr 6q24 (2/3rd cases)
11. LESS COMMON TYPES OF DIABETES IN CHILDREN CONTD...
Mitochondrial diabetes:
o Maternally inherited diabetes
o Associated with sensorineural deafness
o Progressive non-autoimmune beta cell failure
o Presentation : variable
o Acute onset with or without ketoacidosis
o Gradual onset
o Avoid metformin : theoretical risk of severe lactic acidosis
12. LESS COMMON TYPES OF DIABETES IN CHILDREN CONTD...
Cystic fibrosis and diabetes:
o CFRD : Most common comorbidity associated with cystic
fibrosis
o Pathophysiology:
o Insulin deficiency
o Glucagon deficiency
o Insulin resistance (secondary to infections & medications
: bronchodilators, glucocorticoids)
o Others: delayed gastric emptying, altered intestinal
motility, liver disease
o Presentation : Adolescence & early adulthood
13. CYSTIC FIBROSIS AND DIABETES CONTD...
o Onset of CFRD : date a person with CF first meets diabetes
diagnostic criteria , even if hyperglycemia subsequently
abates.
o Poor prognostic sign
o Annual screening:
o Commence by age 10 years in all CF patients who do not
have CFRD
o 2 hr OGTT , 75 gm ( 1.75 g/kg)
14. LESS COMMON TYPES OF DIABETES IN CHILDREN
CONTD...
Stress hyperglycemia:
Associated with acute illness/sepsis; traumatic injuries,
febrile seizures, burns, fever.
Incidence of progression to overt diabetes: 0-32%
15. TYPE 1 DIABETES MELLITUS
Formerly called IDDM or juvenile diabetes
Severe insulinopenia and dependence on exogenous
insulin to prevent ketosis and to preserve life
Onset- childhood (median age 7-15 yrs) but may
present at any age
Autoimmune destruction of pancreatic islet beta cells
Diabetes associated auto antibodies:
1. GAD 2. IA2 3. IAA 4. ZnT8
Clinically symptomatic: destruction of 90% β – cells.
16. Genetic susceptibility
Exposure to unknown
environmental triggers
chance??
Lack of Exposure to
unknown environmental
triggers chance??
No autoimmunityautoimmunity
Progressive beta
cell loss
No apparant
beta cell loss
why??
Clinical diabetes
Clinical remission
(Honeymoon phase)
complications
NO diabetes
18. TYPE 1 DIABETES MELLITUS CONTD...
Environmental factors:
Largely unknown
Enteroviruses
Congenital rubella syndrome
Prenatal infection : beta cell auto immunity in up to 70%
: development of T1DM in up to 40%
Time lag as high as 20 yrs
No increase risk when infection develops after birth.
The hygiene hypothesis
Protective role of infections
Lack of exposure to childhood infections: increase chances
of developing autoimmune diseases including T1DM.
19. TYPE 1 DIABETES MELLITUS CONTD...
Environmental factors contd...
Diet
Breast feeding: decrease risk of T1DM
: directly or delaying exposure to
cow’s milk protein
Psychological stress
The accelerator hypothesis: role of insulin resistance
T1DM and T2DM – same disorder of insulin
resistance, set against different genetic backgrounds.
20. PATHOPHYSIOLOGY
Insulin
causes
Is secreted by
Secretion all mediated by
stimulted by secretion
inhibited by
A polypeptide
hormone
Beta cells of
pancreas
Blood
glucose
epinephrine
glucose uptake
synthesis of
•Glycogen
•Protein
•Fat
Glycogenolysis
Gluconeogenesis
Ketogenesis
lipolysis
Activation of insulin
receptors
22. Normal insulin secretion : interplay of neural, hormonal,
substrate related mechanisms
Normal metabolism : regular swings between post
prandial high insulin anabolic state and fasted low
insulin catabolic state
T1DM : permanent low insulin catabolic state in which
feeding cannot reverse but rather exaggerates these
catabolic processes.
PATHOPHYSIOLOGY CONTD...
23. Liver is more sensitive than muscle or fat to a given
concentration of insulin
With progressive failure of insulin secretion, initial
manifestation is postprandial hyperglycemia.
Fasting hyperglycemia : late manifestation, reflects
severe insulin deficiency and excessive endogenous
glucose production
PATHOPHYSIOLOGY CONTD...
24. Hyperglycemia
Osmotic diuresis (glycosuria when exceeds renal
threshold)
Loss of calories and electrolytes; persistent dehydration
Release of stress hormones (cortisol, glucagon, epinephrine, growth
hormone)
Metabolic decompensation
Decrease insulin secretion(epi)
Antagonizing insulin action(epi,corti,GH)
Promote glyocogenolysis , gluconeogenesis , lipolysis , ketogenesis
( glucagon,epi,GH,corti)
Decrease glucose utilization and glucose clearance (epi,corti,GH)
PATHOPHYSIOLOGY CONTD...
26. PATHOPHYSIOLOGY CONTD...
Accumulation of keto acids
Metabolic acidosis (diabetic ketoacidosis, DKA)
Compensatory rapid deep breathing(kussmaul breathing)
Ketones and cations loss in urine
Further increases water and electrolyte loss
28. CLINICAL MANIFESTATIONS
Initially : limited insulin reserve occasional
hyperglycemia.
When s. glucose increases above renal threshold
Intermittent polyuria or nocturia
Further beta cell loss : chronic hyperglycemia causes
more persistent diuresis with nocturnal enuresis and
polydipsia.
Female patients : monilial vaginitis
29. CLINICAL MANIFESTATIONS CONTD...
Calories loss in urine (glycosuria) triggers
compensatory hyperphagia.
Hyperphagia does not keep pace with glycosuria
loss of body fat weight loss.
Extremely low insulin levels keto acids
accumulate abdominal discomfort, nausea
and emesis.
Dehydration accelerates, polyuria persists
weakness or orthostasis.
30. CLINICAL MANIFESTATIONS CONTD...
Hyperosmotic state : intravascular volume is
conserved at the expense of intracellular volume.
Ketoacidosis exacerbates prior symptoms and leads
to kussmaul respiration, fruity breath odor,
prolonged QTc interval, diminished neurocognitive
function, and possible coma.
31. SYMPTOMS & SIGNS
More Common Less Common Severe (Diabetic
ketoacidosis)
Weight loss Excessive hunger Frequent vomiting and
acute abdominal pain
Polyuria – in younger
children bedwetting is
common
Blurred vision Flushed cheeks
Acetone smell on breath
Excessive thirst Mood changes Dehydration with
continuing polyuria
Tiredness - not want- ing
to work or play
Skin infections Decreased level of
consciousness
Oral or vaginal thrush Kussmaul respiration
(deep, rapid, sighing
Abdominal pain Coma , Shock
32. DIAGNOSTIC DILEMMAS
Sepsis
Asthma/Pneumonia
UTI
Gastroenteritis
Acute abdomen
High index of suspicion if inappropriate polyuria in any child with
dehydration, and poor weight gain.
33. PREDIABETES
Patients with impaired fasting glucose(IFG) and/or
impaired glucose tolerance : referred to as having
‘prediabetes’.
Intermediate stages between normal glucose
homeostasis and diabetes
IFG : measure of disturbed carbohydrate metabolism in
the basal state.
Fasting plasma glucose : 100-125 mg/dl = IFG
IGT : a dynamic measure of carbohydrate intolerance
after a standardized glucose load.
2 hour post load glucose : 140-200 mg/dl = IGT
IFG and IGT are not interchangeable.
34. DIAGNOSITIC CRITERIA (ISPAD/ADA GUIDELINES)
Criteria for the diagnosis of diabetes mellitus
i. Classic symptoms of diabetes with plasma glucose
concentration ≥11.1mmol/L (200mg/dL)
OR
ii. Fasting plasma glucose ≥7.0mmol/L (≥126mg/dL).
OR
iii. Two hour post-load glucose≥11.1mmol/L (≥200mg/dL)
during an OGTT*
OR
iv. ? HbA1c > 6.5%
35. INVESTIGATIONS
Estimation of blood glucose
Sample: 1. whole blood
2. plasma
3. serum
Whole blood values : 10-15% lower than plasma
Lower glucose concentration in erythocytes
Normal range vary with hematocrit.
Plasma preferred.
36. SAMPLE COLLECTION:
Blood is collected into a tube containing sodium fluoride
(NaF) and potassium oxalate (1:3 mixture).
Both the substances act as anticoagulant and NaF
prevents glycolysis in RBCs and WBCs by inhibiting the
enzyme enolase.
37. PRINCIPLE:
GLUCOSE OXIDASE METHOD
measure of true glucose content in body fluids
glucometers as well as autoanalyzers : based on this
principle.
The intensity of the colored product is proportional to
the glucose concentration and is measured
photometrically between 490 and 540 nm.
38. GLUCOMETERS
Test strips: impregnated with glucose oxidase and other
components. Each strip is used once and then discarded
Coding:
manual entry of code into glucometer : calibrate meter
to that batch of strips ( if carried out incorrectly, the
meter reading can be up to 4 mmol/L (72 mg/dL)
inaccurate)
Alternative: strips containing code information or
microchip to be inserted into the meter.
‘Whole blood equivalent’ or ‘plasma equivalent’ values :
plasma equivalent reading using an equation built into
the glucose meter.
40. FOR KETONES : ROTHERA’S NITROPRUSSIDE TEST
Ketonuria is seen in - Diabetic ketoacidosis, Starvation,
Severe vomiting, Glycogen storage disorders and in high fat
diet.
41. KETOSTIX
Principle:
development of colors ranging from buff-pink to
maroon when acetoacetic acid reacts with
nitroprusside.
It does not detect betahydroxybutyrate
45. NEW ONSET DIABETES WITHOUT KETOACIDOSIS
Goals of therapy:
Maintaining tight glycemic control
Avoid hypoglycemia
Eliminate polyuria, and nocturia
Prevent DKA
Allow normal growth & near normal lifestyle
(education, modification in diet, exercise)
46. TREATMENT: INSULIN THERAPY
Insulin Requirements:
Factors:
Body Weight
Age: Pubertal Vs Younger
New onset: Honeymoon phase (residual beta cell
function)
Long standing diabetes: No insulin reserves
47. EXOGENOUS VS ENDOGENOUS INSULIN
Exogenous insulin does not pass through liver unlike
pancreatic insulin
Hypoglycemia can occur with exogenous insulin unlike
endogenous insulin release which can be inhibited with
onset of hypoglycemia
Exogenous insulin absorption affected by site of
injection Vs endogenous insulin which is directly
released into portal circulation.
48. TYPES OF INSULIN FOR USE IN T1DM
Insulin Type (trade name) Onset Peak Duration
Bolus (prandial) Insulins
Rapid-acting insulin analogues (clear):
• Insulin aspart (NovoRapid®)
• Insulin glulisine (Apidra™)
• Insulin lispro (Humalog®)
10 - 15 min
10 - 15 min
10 - 15 min
1 - 1.5 h
1 - 1.5 h
1 - 2 h
3 - 5 h
3 - 5 h
3.5 - 4.75 h
Short-acting insulins (clear):
• Insulin regular (Humulin®-R)
• Insulin regular (Novolin®geToronto)
30 min 2 - 3 h 6.5 h
Basal Insulins
Intermediate-acting insulins (cloudy):
• Insulin NPH (Humulin®-N)
• Insulin NPH (Novolin®ge NPH)
1 - 3 h 5 - 8 h Up to 18 h
Long-acting basal insulin analogues
(clear)
• Insulin detemir (Levemir®)
• Insulin glargine (Lantus®)
90 min Not
applicable
Up to 24 h
(glargine 24 h,
detemir 16 - 24 h)
49.
50. INSULIN REGIMENS
Basal-bolus Regimen: Slow onset, long duration
background insulin for b/w meal glucose control and
rapid onset insulin at each meal
X Twice daily insulin: NPH combined with regular insulin
(70/30, 75/25): No longer preferred: Peaks with NPH &
Lente leading to hypoglycemia; Unpredicatable
interaction with plain insulin
X Lente and ultralente no longer available
51. NPH AND REGULAR(MIXED-SPLIT)
Advantages
2-3 shots per day
“Easier” – less carb counting and calculations
Disadvantages
Strict dietary plan
Less flexible
Less physiologic
52. BASAL/BOLUS
Advantages
More physiologic
More flexible
Less hypoglycemia
Disadvantages
More labor-intensive (CHO counting, insulin
calculations)
At least 4 injections per day
53. DIABETES CONTROL AND COMPLICATIONS TRIAL
1983-1993, early termination given results
Intensive therapy delays onset and progression of long-term
complications in type 1 diabetes
Conventional Therapy Intensive Therapy
1-2 injections/day ≥3 injections/day
Mean A1c 9% Mean A1c 7%
54. APPROXIMATE DAILY INSULIN REQUIREMENTS
Pre-pubertal 0.7 U/kg/d
Mid-pubertal 1.0 U/kg/d
End of pubertal 1.2 U/kg/d
55. INITIATING THERAPY IN A CHILD NOT IN DKA
Day 1
Give short-acting (regular) insulin (0.1 U/kg) every
second hour until blood glucose is < 11 mmol/l(200
mg/dL), then every 4-6 hours.
If hourly monitoring of blood glucose cannot be
provided, begin with half the above dose.
Day 2 (from morning/breakfast):
Total daily dose 0.5-0.75U/kg/day.
56. A. TWO INJECTIONS PER DAY
1. A starting point is to give two-thirds of the total daily
insulin in the morning before breakfast and one-third
before the evening meal.
2. On this regimen, at the start, approximately one-third
of the insulin dose may be short-acting (regular)
insulin and approximately two-thirds may be
intermediate-acting insulin.
57. EXAMPLE
For a 36 kg child who is started on 0.5 U/kg/day, the
total daily dose is 18 Units. Two-thirds of this is given in
the morning (before breakfast) – (12 Units), and one-
third before the evening meal – 6 Units. At each
injection, 1/3 is short-acting and 2/3 is intermediate-
acting.
Short acting Intermediate
acting
Before breakfast 4 Units 8 Units
Before evening
meal
2 Units 4 Units
58. REMEMBER
For mixed insulin, always think of the components
separately (i.e. 10 units of mix 30/70 equals 3 units of
short-acting (regular) and 7 units of intermediate-acting
(NPH)), and adjust doses as above.
59. B. BASAL BOLUS REGIMEN
If short-acting (regular) and intermediate-acting insulin
70% of the total daily dose as short-acting (regular) insulin
(divided up between 3-4 pre-meal boluses)
PLUS
30% of the total daily dose as a twice daily injection of
intermediate-acting insulin
If short-acting (regular) and long-acting analogue insulins:
50% of the total daily dose as short-acting (regular) insulin
(divided up between 3-4 pre-meal boluses)
PLUS
50% of the total daily dose as a single evening injection of long-
acting analogue insulin. (Sometimes this dose does not last for
24 hours and then can be split into two doses morning and
evening).
60. BASAL/BOLUS
I:CHO = 450/total daily insulin dose = amount of carbs 1
units will cover
Correction Factor (adjustment of insulin dose based on
blood glucose): “1800 rule” = 1800/TDD
Glargine can not be mixed with any other insulins
61. INSULIN DOSE ADJUSTMENTS
Subsequently, doses can be adjusted daily according to
blood glucose levels
1 U of rapidly acting insulin can drop blood sugar by 50
mg/dL
Adjustments needed as child returns to daily activities:
Insulin requirements decrease
Adjustments also once diet modifications made
62. RECOMMENDED TARGET BLOOD GLUCOSE LEVELS:
Before meals 4-7 mmol/l (72-126 mg/dl)
After meals 5-10 mmol/l (90-180 mg/dl)
At bed time 6-10 mmol/l (108–180 mg/dl)
At 3am 5-8 mmol/l (90-144 mg/dl)
63. FACTORS AFFECTING TITRATION
The level of blood glucose can rise in the early
morning (“dawn phenomenon”) and so care should
taken if increasing the evening intermediate/long-
acting dose as hypoglycemia can occur in the middle
of the night and this can be dangerous.
Insulin requirements can decrease for a time during
the “honeymoon period” before rising again.
The total daily dose required will generally increase
as the child grows, and once puberty ensues a higher
dose per kg per day is often needed.
64. MIXING INSULINS IN THE SAME SYRINGE
Common to combine intermediate-acting and short-
acting/rapid-acting insulins, to cover both basal needs
plus the extra need from eating. Can be combined in the
same syringe.
Begin by injecting air into both bottles. The short-acting
insulin is generally drawn into the syringe first.
If the intermediate-acting insulin is a “cloudy” insulin,
mix by tipping the vial/bottle up and down 10 – 20
times. Do not shake the insulin as this damages the
insulin. The doses can be adapted every day according
to food intake, physical activity, and blood glucose
readings.
65. GIVING AN INJECTION WITH A SYRINGE
Insulin syringes ( needle < 8mm) made for correct strength of insulin (U-
100 or U-40), adequate gradations
Check the expiry date, and the name (correct amount of the correct
insulin)
Pull the plunger down to let air in the syringe, equalling the amount of
insulin to be given. Inject this air into the vial.
Draw up the insulin
Take a small pinch of skin with the index finger and thumb. The pinch
needs to be at least to the depth of the needle. This is especially important
in lean people, otherwise the injection may go too deep into the muscle
layer, hurt more, and absorption will be affected.
Insert the needle at a 45 degree angle into the pinched-up skin to a
distance of 4-6 mm. Give the injection.
Leave the needle in for about 5-10 seconds, then gradually let go of the
skin and pull out the needle.
Dispose of the syringe appropriately depending on local advice e.g. sharps
container, tin, or strong plastic bottle.
67. INJECTION SITES
1. Good technical skill concerning
syringes/ pens
2. Injections in the abdominal area
preferred ,evenly absorbed , less
affected by exercise
3. Children and adolescents
encouraged to inject consistently within
the same area (abdomen, thing,
buttocks) at a particular time of day, but
must avoid injecting repeatedly into the
same spot to avoid lipohypertrophy.
68. INSULIN STORAGE
Store at 4-8 deg. C in a refrigerator
In hot climates where refrigeration not available, cooling
jars, earthenware pitcher (matka) or a cool wet cloth
around the insulin.
Insulin must never be frozen.
Avoid direct sunlight or extreme heat (in hot climates or
in a vehicle)
Dont use insulins that have changed in appearance
(clumping, frosting, precipitation, or discolouration).
After first usage, an insulin vial should be discarded after
3 months if kept at 2-8 deg.C or 4 weeks if kept at room
temperature.
69. INSULIN THERAPY
If initial regimen fails to meet glycemic targets, more
intensive management may be required:
Three methods of intensive diabetes management can
be used at any age:
Similar regimen with more frequent injections
basal bolus regimens using long and rapid acting insulin
analogues
continuous subcutaneous insulin infusion (CSII, insulin pump
therapy)
70. GLYCEMIC TARGETS
Age (years) A1C (%) FPG / premeal
PG
(mg/dL)
Considerations
<5 7.5- 9.0% 100-200 Caution is required to minimize
hypoglycemia because of the potential
association between severe hypoglycemia
and later cognitive impairment. Consider
target of <8.5% if excessive hypoglycaemia
occurs
5-11 6.5-8.0% 150-200 Targets should be graduated to the child’s
age. Consider target of <8.0% if excessive
hypoglycaemia occurs
12-15 6.0-7.5% 120-180 Appropriate for most adolescents
*Postprandial monitoring is rarely done in young children except for those on pump
therapy for whom targets are not available
A1C = Glycated Hemoglobin; FPG = Fasting Plasma Glucose; PG = Plasma Glucose; N/A
= Not Available
71. GLYCEMIC TARGETS
Children with persistently poor glycemic control (e.g.
A1C >10%) should be assessed by a specialized pediatric
diabetes team for a comprehensive interdisciplinary
assessment and referred for psychosocial support as
indicated . Intensive family and individualized
psychological interventions aimed at improving
glycemic control should be considered to improve
chronically poor metabolic control.
72. CHRONIC POOR METABOLIC CONTROL
Diabetes control may worsen during adolescence,
possibly due to the following factors:
Adolescent adjustment issues
Psychosocial distress
Intentional insulin omission
Physiologic insulin resistance
73. INSULIN THERAPY
It is reasonable to introduce a basic insulin regimen (e.g.
minimum 3 injections per day) but a more intensive
system is indicated if success not achieved despite good
effort
Insulin Pump
Therapy
Low Glucose
Suspend
Sensor Augmented
Insulin Pump
74. HONEYMOON PHASE
Educate that it may happen
Diabetes is not cured!
Occurs within first 3 months of diagnosis
Insulin requirements <0.5 units/kg/day
Lasts weeks to up to 2 years
Resolution of glucotoxicity, recovery of residual β-cell
function
76. INSULIN PUMP THERAPY-CONTINUOUS SUBCUTANEOUS
INSULIN INFUSION (CSII).
Alternative to treatment with MDI if HbA1c is
persistently above the individual goal , hypoglycemia is a
major problem or quality of life needs be improved
More physiological insulin replacement therapy
Newer generation of ‘‘smart’’ pumps automatically
calculate meal or correction boluses based on insulin-to-
carbohydrate ratios
Rapid acting analog insulins are used in most pumps
Motivation appears to be a crucial factor for the long-
term success of this form of therapy
78. INSULIN PUMP
Only NovoLog or Humalog insulin
Hourly basal rate:
1. 80% of total daily insulin dose
2. Divided by 2
3. Divide by 24
Same I:CHO and correction factor
79. INSULIN PUMP
Advantages
Mimics physiologic pancreatic secretion
Lifestyle
Accurate dosing
Less hypoglycemia
Disadvantages
No depot to protect from DKA
Labor intensive
Expensive
80. INHALED & ORAL INSULIN THERAPY
Inhaled insulin (EXUBERA) -This new form of insulin
therapy investigated in children above 12 years of age as
part of a study in adults , not approved for clinical use in
children. The sale of inhaled insulin discontinued in
2007.
Oral insulin(ORALIN)-evaluated in comparison with
OHA, mostly in T2DM , data appears promising but
further evaluation in T1DM needed.
81. GLUCOSE MONITORING
Self-monitoring of blood glucose is an essential part of
management of type 1 diabetes
Subcutaneous continuous glucose sensors allow
detection of asymptomatic hypoglycemia and
hyperglycemia
Subcutaneous continuous glucose sensors may have a
beneficial role in children and adolescents but evidence
is not as strong as in adults
82. GLYCOSYLATED HEMOGLOBIN(HBA1C)
Glucose nonenzymatically attached to hemoglobin
during the life cycle of the circulating RBCs (HbA1 or
HbA1c)
HbA1c reflects levels of glycemia over the preceding 4–
12 wk, weighted toward the most recent 4 wks
A target range for all age-groups <7.5% is recommended
83. FRUCTOSAMINE AND OTHER GLYCATED PRODUCTS
Fructosamine measures the glycation of serum proteins
such as albumin and reflects glycemia over the
preceding 3–4 wk
Used for assessment of shorter periods of control than
HbA1c.
Fructosamine or glycated albumin useful in individuals
with abnormal red cell survival time.
Fructosamine and other glycated products have not
been evaluated in terms of later vascular risk.
84. COMPLICATIONS OF INSULIN THERAPY
Hypoglycemic Reactions
Hyperglycemic episodes
Somogyi Phenomenon
Dawn Phenomenon
Brittle Diabetes
85. HYPOGLYCEMIA ( BGL < 70 MG/DL)
All families should understand the importance of
hypoglycemia (severity and frequency) along with
treatment and follow up strategies
86. HYPOGLYCEMIA – KEY MESSAGE
Hypoglycemia is a major obstacle for children with type
1 diabetes and can affect their ability to achieve
glycemic targets
Significant risk of hypoglycemia often necessitates less
stringent glycemic goals, particularly for younger
children
There is no evidence in children that one insulin regimen
or mode of administration is superior to another for
reducing non-severe hypoglycemia.
87. EXAMPLES OF CARBOHYDRATE FOR TREATMENT OF MILD TO
MODERATE HYPOGLYCEMIA
Patient Weight <15 kg 15 to 30 kg >30 kg
Amount of carbohydrate 5g 10 g 15 g
Carbohydrate Source
Glucose tablet (4 g) 1 2 or 3 4
Dextrose tablet (3 g) 2 3 5
Apple or orange juice; regular
soft drink; sweet beverage
(cocktails)
40 ml 85 ml 125 ml
88. HYPOGLYCEMIA
Frequent use of continuous glucose monitoring in a
clinical care setting may reduce episodes of
hypoglycemia
In children, the use of mini-doses of glucagon has been
shown to be useful in the home management of mild or
impending hypoglycemia associated with inability or
refusal to take oral carbohydrate
Dose = 10 mcg x (years of age)
Dose range 20 – 150 mcg
89. RECOMMENDATION
In the home situation, severe hypoglycemia in an
unconscious child >5 years of age should be treated
with 1 mg of glucagon subcutaneously or
intramuscularly. In children ≤5 years of age, a dose of
0.5 mg of glucagon should be given. The episode should
be discussed with the diabetes healthcare team as soon
as possible and consideration given to reducing insulin
doses for the next 24 hours to avoid further severe
hypoglycemia
90. RECOMMENDATION
Dextrose 0.5 to 1g/kg (5-10 ml/kg of 10% D) should be
given over 1 to 3 minutes to treat severe hypoglycemia
with unconsciousness when IV access is available
91. DAWN & SOMOGYI PHENOMENON
Dawn phenomenon-
Overnight GH secretion & insulin clearance
Normal physiological process in nondiabetic
adolescents(compensate with more insulin
output),T1DM cant compensate
Somogyi phenomenon
A theoretical rebound from late night or early morning
hypoglycemia
Uncommon, counterregulatory response
92. BRITTLE DIABETES
Unexplained wide fluctuations in blood glucose
Recurrent DKA (though on large doses of insulin)
Inherent physiological abnormality rarely a cause
Psychosocial or psychiatric problems contribute
Clinicians to refrain using it as a diagnostic term
93. SICK DAY MANAGEMENT
Never omit insulin
Insulin requirements are often greater with illness
Hypoglycemia may be a problem, especially in younger
children
Test blood sugars every 2-4 hours
Check urine ketones
94. SICK DAY MANAGEMENT
Drink plenty of fluids (1 cup per hour)
Sugar-containing liquids for hypoglycemia
Need extra insulin to clear ketones
NPH/R: extra 20% of total dose as R q4 hours
Basal/bolus: correction dose q3 hours + additional
20% of calculated correction
ED for persistent vomiting
95. NUTRITION
Healthy, balanced diet
50-60% total calories from carbohydrate
<30% fat
10-20% protein
Carbohydrate counting
No forbidden foods - moderation
Eating too much will not cause ketosis
BF (20%) + L (20%) + D (30%) + 3 b/w meal snacks (10%
each)
96. EXERCISE
Increases sensitivity to insulin
Helps control blood sugar
Lowers cardiovascular risk
Blood sugar usually decreases but may initially increase
Hypoglycemia may occur during, immediately after, or 8-
24 hours later
May need extra snacks or decreased insulin (learn from
experience)
Usually 15 gm CHO for every 30 min vigorous exercise
Do not exercise if ketones are present
98. RECOMMENDATIONS
Influenza immunization should be offered to children
with diabetes as a way to avoid an intercurrent illness
that could complicate diabetes management
Formal smoking prevention and cessation counselling
should be part of diabetes management for children
with diabetes.
Adolescent females with type 1 diabetes should
receive counselling on contraception and sexual
health in order to avoid unplanned pregnancy
99. RECOMMENDATIONS
Children and adolescents with diabetes, along with
their families, should be screened regularly for
psychosocial or psychological disorders and should be
referred to an expert in mental health and or
psychosocial issues for intervention when required
Adolescent females with type 1 diabetes should be
regularly screened using nonjudgmental questions
about weight and body image concerns, dieting, binge
eating, and insulin omission for weight loss
100. COMORBID ASSOCIATIONS
Always consider the possibility of autoimmune thyroid
and adrenal disease, and celiac disease, particularly
when there are suggestive signs or symptoms
101. SCREENING FOR COMORBID CONDITIONS
Condition Indications for screening Screening test Frequency
Autoimmune
thyroid disease
All children with type 1
diabetes
Serum TSH level +
thyroperoxidase
antibodies
At diagnosis and every
2 years thereafter
Positive thyroid antibodies,
thyroid symptoms or goiter
Serum TSH level +
thyroperoxidase
antibodies
Every 6–12 months
Addison’s
disease
Unexplained recurrent
hypoglycemia and
decreasing insulin
requirements
8 AM serum cortisol
+ serum sodium and
potassium
As clinically indicated
Celiac disease Recurrent gastrointestinal
symptoms, poor linear
growth, poor weight
gain, fatigue, anemia,
unexplained frequent
hypoglycemia or poor
metabolic control
Tissue
transglutaminase
+ immunoglobulin A
levels
As clinically indicated
102. DIABETES CHRONIC COMPLICATIONS
Nephropathy, retinopathy, neuropathy and hypertension
are relatively rare in pediatric diabetes
Screening efforts should focus most attention on post-
pubertal patients with longer duration and poorer
control of their diabetes
103. Complication Indications & intervals for
screening
Screening method
Nephropathy •Yearly screening commencing
at 12 years of age in those with
duration of type 1 diabetes ≥ 5
years (ACR-alb/creatinine ratio)
• First morning (preferred) or random ACR
• Abnormal ACR requires confirmation at least 1
month later with a first morning ACR, and if
abnormal, followed by timed, overnight or 24-
hour split urine collections for albumin
excretion rate
• Repeated sampling should be done every 3–
4 months over a 12-month period to
demonstrate persistence
Retinopathy •Yearly screening commencing
at 15 yrs of age with duration of
DM ≥ 5 yrs
• Screening interval can
increase to 2 yrs if good
glycemic control, duration of
diabetes < 10 yrs, and no
retinopathy at initial
assessment
• 7-standard field, stereoscopic-colour fundus
photography with interpretation by a trained
reader (gold standard); or
• Direct ophthalmoscopy or indirect slit-lamp
fundoscopy through dilated pupil; or
• Digital fundus photography
104. Complication Indications & intervals for
screening
Screening method
Neuropathy • Postpubertal adolescents with
poor metabolic control should
be screened yearly after 5
years’ duration of DM
• Question and examine for
symptoms of numbness, pain,
cramps and paresthesia, as well
as sensation, vibration sense,
light touch & ankle reflexes
Dyslipidemia • Delay screening post-
diabetes diagnosis until
metabolic control has
stabilized
• Screen at ≥12 years of age or
<12 years of age with BMI >
95th percentile, family history
of hyperlipidemia or premature
CVD
• Fasting total cholesterol,
high-density lipoprotein
cholesterol, triglycerides,
calculated low-density
lipoprotein cholesterol
Hypertension • Screen all children with
type 1 diabetes at least twice
a year
• Use appropriate cuff size
105. ADULT VS CHILD DIABETES
Guidelines for children and adolescents differ from those of
adults in a number of ways:
Less aggressive A1C target acceptable in younger children
Less intensive screening for complications of diabetes in the
younger years due to lower incidence
Greater caution around DKA management given cerebral
edema risk
Greater awareness of unique psychosocial needs as children
progress through developmental stages
106. DIABETIC KETOACIDOSIS (DKA)
Medical emergency
Profound insulin deficiency
Can be
the 1st presentation of T1DM
In children with diabetes if insulin is omitted
Insufficient insulin at times of acute illness
107. BIOCHEMICAL CRITERIA FOR DKA
Hyperglycaemia (blood glucose >11mmol/l (~200
mg/dl))
Venous pH <7.3 or bicarbonate <15 mmol/l
Ketonemia and ketonuria
blood β- hydroxybutyrate (BOHB) concentration should
be measured whenever possible;
a level ≥3mmol/L : indicative of DKA
Euglycemic ketoacidosis : only modestly increased blood
glucose in partially treated or with little or no
carbohydrate consumption.
108. SEVERITY OF DKA
Mild : venous pH<7.3 or bicarbonate <15mmol/L
Moderate : pH<7.2, bicarbonate <10mmol/L
Severe : pH<7.1, bicarbonate <5mmol/L.
109. DKA PROTOCOL : MILWAUKEE PROTOCOL
Time Therapy Comments
1st hour •10-20 ml/kg IV bolus NS or RL
•Insulin drip at 0.05-0.1 u/kg/hr
Quick volume expansion; may
be repeated. Continuous
monitoring.
Mannitol at bedside; 1g/kg iv
push for cerebral edema
2nd hour
until DKA
resolution
•0.45% NS : plus continue insulin
drip
•20 m Eq/l Kphos and 20 mEq/l Kac
•5% glucose if BG> 250 mg/dl
IV rate=
85ml/kg+maintainence-bolus
23 hours
If K <3mEq/l, give 0.5-1
mEq/kg(oral)
OR increase IV K to 80 mEq/l
Variable Oral intake with s/c insulin No emesis; CO2 > 16 mEq/l;
normal electrolytes.
110. DKA PROTOCOL : MILWAUKEE PROTOCOL CONTD...
Maintenance (24 hrs)= 100 ml/kg(1st 10 kg) + 50
ml/kg(for 2nd 10 kg) + 25 ml/kg (for remaining kg)
Example: 30 kg child
1st hour : 300 ml iv bolus NS or RL
2nd and subsequent hours: (85x 30) + 1750 – 300 over
23 hours
(0.45% NS with 20 mEq/l Kphos and 20 mEq/l KAc )
112. ISPAD CLINICAL PRACTICE CONSENSUS GUIDELINES
2014
Accepted and supported by:
Law- son Wilkins Paediatric Endocrine Society (LWPES)
European Society for Paediatric Endocrinology (ESPE),
and
International Society for Paediatric and Adolescent
Diabetes (ISPAD)
113. COMPONENTS OF MANAGING DKA (ISPAD 2014)
1. Initial assessment and monitoring
2. Correction of shock
3. Correction of fluid replacement
4. Insulin treatment
5. Potassium replacement
6. Role of bicarbonate
7. Treatment of infection (if present)
8. Management of cerebral oedema
9. Monitoring of the child
10. Transitioning to subcutaneous insulin
114. INITIAL ASSESSMENT AND MONITORING:
Clinial assessment: history, examination. Include:
Severity of dehydration. If uncertain assume 10%
dehydration in significant DKA
1 mnth -5 yrs age: 3 important signs to predict 5%
dehydration
Prolonged CRT
Abnormal skin turgor
Abnormal respiratory pattern(hyperpnea)
>10% dehydration: weak or impalpable peripheral
pulses, hypotension and oliguria.
115. INITIAL ASSESSMENT AND MONITORING CONTD...
Level of consciousness
Evidence of infection
Weight of the child
Measure blood glucose ( both glucometer and lab)
Measure ketones by urine dipstick (and blood ketone
measurement if possible)
Other investigations:
1. Serum electrolytes 4. KFT
2. CBC 5. microbiological samples
3. ABG/VBG: pH, HCO3 6. HbA1c
116. INITIAL ASSESSMENT AND MONITORING CONTD...
Monitor:
Record hourly : heart rate, blood pressure, respiratory
rate, level of consciousness, glucose meter reading
Monitor urine ketones in every sample of urine passed
Record fluid intake, insulin therapy and urine output
Repeat blood urea and electrolytes every 2-4 hours
117. CORRECTION OF SHOCK
Ensure A, B, C
Oxygen support
Resuscitation fluids:
severely volume depleted but not in shock : NS @
10-20 ml/kg over 1-2 h
DKA in shock : NS in 20 ml/kg boluses infused as
quickly as possible with reassessment after each
bolus.
Shock must be adequately treated before proceeding
118. FLUID REPLACEMENT
Subsequent fluid management (deficit replacement) :
with an isotonic solution ( NS, RL) for atleast 4–6 h
Deficit replacement after 4–6 h : with a solution of
tonicity ≥0.45% saline with added potassium chloride,
potassium phosphate.
The decision to change from an isotonic to a
hypotonic solution depends on the patient’s
hydration status, serum Na, and osmolality
Aim to provide maintenance and deficit replacement
(up to 10%) over 48 hours.
119. FLUID REPLACEMENT CONTD...
This volume should be distributed evenly over the 48
hours.
Do not add the urine output to the replacement volume
Reassess clinical hydration regularly
Once BGL <15 mmol/l (<270 mg/dl), add dextrose to the
saline
add 100ml of 50% dextrose to every litre of saline, or
use 5% dextrose saline
120. INSULIN TREATMENT
It should be started 1-2 hours after initiating fluid
therapy
earlier onset of insulin treatment has been associated with
cerebral oedema.
Insulin is best given intravenously by an infusion.
Intravenous infusion of 0.05-0.1 unit/kg/hour.
given in two ways:
A. Using a syringe pump - dilute 50 units short-acting
(regular,soluble) insulin in 50 ml NS, 1 unit = 1 ml). OR
B. Use a side drip - put 50 Units of short-acting (regular)
insulin in 500 ml of NS ( 1 Unit = 10ml).
121. INSULIN TREATMENT CONTD...
An IV bolus should not be used at the start of therapy
Unnecessary
Increase risk of cerebral edema
Exacerbate hypokalemia
If insulin cannot be given intravenously by a side drip or
infusion pump, use deep subcutaneous or intramuscular
insulin:
Give 0.1 unit/kg of short-acting (regular, soluble) or rapid-
acting insulin SC or IM into the upper arm, and repeat this
dose every 1-2 hours.
122. INSULIN TREATMENT CONTD...
The dose of insulin should usually remain at 0.05–
0.1unit/kg/h at least until resolution of DKA
i.e. pH>7.30, bicarbonate >15mmol/L, BOHB <1mmol/L,
or closure of the anion gap),
which invariably takes longer than normalization of BG
concentrations.
123. POTASSIUM REPLACEMENT
Potassium replacement is needed for every child in DKA.
Blood potassium level : initial assessment
If potassium levels cannot be done, ECG monitoring
Hypokalaemia : Flattening of the T wave, widening of the QT
interval and the appearance of U waves .
Hyperkalaemia : Tall, peaked, symmetrical T waves and
shortening of the QT interval.
Ideally start replacing potassium once the serum
potassium value is known or urine output has been
documented. If this value cannot be obtained within 4
hours of starting insulin therapy, start potassium
replacement anyway.
124. POTASSIUM REPLACEMENT CONTD...
Replace by adding KCl to the IV fluids @ 40mmol/L.
Increase according to measured potassium levels.
The maximum recommended rate of intravenous
potassium replacement : 0.5 mmol/kg/hour
If given with the initial rapid volume expansion,
concentration of 20 mmol/l should be used
If hypokalaemia persists despite maximum rate ,the rate
of insulin infusion can be reduced.
125. ROLE OF BICARBONATE:
Severe acidosis is reversible by fluid and insulin.
Bicarbonate therapy:
No clinical benefit
Paradoxical CNS acidosis
Rapid correction causes hypokalemia
Role in life threatening hyperkalemia : 1-2 mmol/kg
over 60 min
126. TREATMENT OF INFECTION
Difficult to exclude infection in DKA : increase TLC due to
stress and acidosis.
Fever : more reliable sign
Treat with broad spectrum antibiotics.
127. CEREBRAL OEDEMA
Rare but often fatal complication of DKA.
Cause : controvertial
can be idiosyncratic
may be related to factors : degree of hyperglycaemia,
acidosis, dehydration and electrolyte disturbance at
presentation, as well as over-rapid correction of
acidosis, dehydration or hyperglycaemia.
129. CEREBRAL OEDEMA CONTD...
If cerebral oedema is suspected TREAT URGENTLY:
Exclude hypoglycaemia as a cause of the change in
neurological state.
Reduce the rate of fluid administration by one third
Give mannitol 0.5-1 g/kg IV over 20 minutes, and re-
peat if there is no initial response in 30 minutes to 2
hours.
Hypertonic saline (3%) 5ml/kg over 30 minutes may be
an alternative to mannitol, esp if there is no initial
response to mannitol
130. CEREBRAL OEDEMA CONTD...
Elevate the head of the bed
Intubation : impending respiratory failure
After treatment has been started, a cranial CT scan to
rule out other possible intracerebral causes of
neurological deterioration
especially thrombosis or haemorrhage
Cerebral oedema is an unpredictable complication of
DKA.
Survivors are often left with significant neurological
deficits.
131. MONITORING THE CHILD
If no improvement in biochemical parameters of DKA
(pH, anion gap, urine ketones):
reassess patient
review insulin therapy
consider infection or errors in insulin preparation.
Consider possibility of serious infection (such as
malaria) with stress hyperglycaemia rather than
diabetes.
132. TRANSITIONING TO SUBCUTANEOUS INSULIN:
Once the DKA has been adequately treated (hydration
corrected, glucose controlled, ketones cleared) the child
can be transitioned to subcutaneous insulin.
The first SC dose of short-acting insulin: 1-2 hours before
stopping the insulin infusion.
easier to transition to subcutaneous insulin at the next
mealtime
