Type I DM in Pediatric

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Type I DM in Pediatric

• Prepared by
• Dr Moslah Jabari
• Pediatric Endocrinologist
• Assistant Professor in Pediatrics

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• Introduction
• Insulin regimen
• Insulin dose
• Diet
• Monitoring
• Hypoglycemia
• Management during infection
• Management during surgery
• Screening for chronic complication

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DIAGNOSTIC CRITERIA FOR IMPAIRED GLUCOSE
TOLERANCE AND DIABETES MELLITUS
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Diagnostic Criteria of Impaired Glucose Tolerance
and Diabetes Mellitus Table

Symptoms include polyuria, polydipsia, and
unexplained weight loss with glucosuria and
ketonuria. A fasting glucose concentration of 99
mg/dL is the upper limit of normal.
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Etiologic Classification of Diabetes Mellitus
Table

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Epidemiology

• The incidence among school-age children is
• about 1.9/ 1,000 in USA with annual incidence
• about 14.9 new cases/ 100,000 children.
• Sex MF ratio is 11.
• Age at presentation Peaks occur in 2 age groups.
  
• At 5-7 yr of age and puberty
• Seasonal variations More frequent in the autumn
  and winter months.

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Etiology

• The Mechanisms that lead to failure of
• pancreatic ß-cell function increasingly point
• to an auto immune destruction of
• pancreatic islet ß cells in predisposed
• individuals.

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Evidences supporting the auto immune basis of
type 1 DM (T1DM)

• Type 1 DM is commonly associated with auto immune
  diseases as celiac disease, Addison disease, and
  thyroiditis.
• 2. Auto antibodies as (GAD)and islet cell
  cytoplasm antibodies (ICA) and insulin auto
  antibodies (IAA) are detected in the sera of
  newly diagnosed patients.

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Evidences supporting the auto immune basis of
type 1 DM (T1DM)

• 3. Genetic predisposition (the increased
  protection and susceptibility to T1DM)
• The Genetics of type 1 DM cannot be
  classified according to a specific model of
  inheritances. The most important genes are
  located within the MHC HLA class II region on
  chromosome 6p21, accounting for about 60 of
  genetic susceptibility for the disease.

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Evidences supporting the auto immune basis of
type 1 DM (T1DM)

• The inheritance of HLA-DR3 or DR4 antigens
  (susceptibility haplotypes) increases the risk
  for developing type 1 DM two to 3 folds. The
  inheritance of both antigens increases the risk
  7-10 fold.
• b. Role of HLA Class Certain alleles of class
  II HLA genes appear to have the strongest
  associations with diabetes, the most significant
  association is with HLA-B39, which confers high
  risk for type 1A diabetes.

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Evidences supporting the auto immune basis of
type 1 DM (T1DM)

• c. The inheritance of certain genotype
• HLA-DRB1-0401
• DQB1-302
• DQA1-0301 confer high risk susceptibility.
• d. The inheritance of certain genotype provide
  significant protection as
• HLA-DRB1-0403
• DQB1-0301
• DQA1-0102

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Evidences supporting the auto immune basis of
type 1 DM (T1DM)

• The homozygous absence of aspartic
• acid at position 57 of the HLA-DQ ß-chain
• confers about 100 fold relative risk for the
• development of T1DM.
• e. Insulin gene locus It is found to be
  associated with risk of T1DM and it is estimated
  that this locus accounts for about 10 of the
  familiar risk of T1DM.

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Evidences supporting the auto immune basis of
type 1 DM (T1DM)

• 4. Environment
• Factors such as viral infections, chemicals,
  seasonal factors, and dietary factors have been
  suspected of contributing to differences in the
  incidence and prevalence of type 1 DM in various
  ethnic populations.

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Evidences supporting the auto immune basis of
type 1 DM (T1DM)

• a. Viral Infections A variety of viruses and
  mechanisms may contribute to the development of
  T1DM in genetically susceptible hosts.
  Enteroviral, congenital rubella, and mumps
  infection leads to the development of ß-cell auto
  immunity with high frequency and to T1DM in some
  cases. Congenital rubella infection is associated
  with diabetes (up to 40).

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Evidences supporting the auto immune basis of
type 1 DM (T1DM)

• b. Diet
• Breast-feeding
• May lower the risk of T1DM, either directly or
  by delaying exposure to cows milk protein.

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Evidences supporting the auto immune basis of
type 1 DM (T1DM)

• Early introduction of cows milk protein and
  early exposure to gluten in cereals have both
  been implicated in the development of auto
  immunity and it has been suggested that this is
  due to the leakiness of the immature gut to
  protein antigen
• s. Antigens that have been implicated include
  ß-lactoglobulin, which is homologous to the human
  protein glycodelin (PP14), a T-cell modulator.
  Other studies have focused on bovine serum abumin
  as the inciting antigen,.

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Evidences supporting the auto immune basis of
type 1 DM (T1DM)

• Other dietary factors that have been suggested at
  various times as playing a role in diabetes risk
  include Omega-3 fatty acids, Vitamin D, ascorbic
  acid, zinc, and Vitamin E
• Vitamin D has a role in immune regulation,
  decreased Vitamin D levels in pregnancy or early
  childhood may be associated with diabetes risk
  but the evidence is not yet conclusive.

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Evidences supporting the auto immune basis of
type 1 DM (T1DM)

• c. Psychologic stress Several studies show an
  increased prevalence of stressful psychologic
  situations among children who subsequently
  developed T1DM. Whether these stresses only
  aggravate pre-existing auto immunity or whether
  they can actually trigger auto immunity remains
  unknown.

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Pathogenesis and natural history of type 1
diabetes mellitus

• A genetically susceptible host develops auto
  immunity against his or her own ß cells. What
  triggers this auto immune response remains
  unclear at this time. In some ( But not all)
  patients, this auto immune process results in
  progressive destruction of ß cells until a
  critical mass of ß cells are destroyed and the
  patient becomes totally dependent on exogenous
  insulin for survival.

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Pathogenesis and natural history of type 1
diabetes mellitus

• 1.Initiation of auto immunity.
• 2. Preclinical auto immunity with progressive
• loss of ß-cell function.
• 3. Onset of clinical disease.
• 4. Transient remission (honeymoon period).
• 5. Established disease.
• 6. Development of complications.

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Pathophysiology

• In normal individuals, there are normal swings
  between the postprandial, high-insulin anabolic
  state and fasted, low-insulin catabolic state
  that affect 3 major tissues liver, muscle, and
  adipose tissue.

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Influence of feeding (High Insulin) or of fasting
(Low Insulin) on some Metabolic processes in
liver, muscles and adipose tissue.
Tissue Postprandial State (High Plasma Insulin) Fasted State (Low Plasma Insulin)
Liver Glucose uptake, glycogen synthesis, absence of gluconeogenesis Lipogenesis Absence of ketogenesis Glucose production (glycogenolysis gluconeogenesis) Absence of lipogenesis Ketogenesis
Muscle Glucose uptake and oxidation, and glycogen synthesis Protein synthesis Absence of glucose uptake Glycogenolysis Proteolysis and amino acid release
Adipose Tissue Glucose uptake Triglyceride uptake Lipid synthesis Absence of glucose uptake Absence of triglyceride uptake Lipolysis and fatty acids release
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• Hyperglycemia- (fasting and increases after
  eating) due to glucose production
  (glycogenolysis and gluconeogenesis) and absence
  of glucose uptake by muscle and adipose tissues.

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• Glucosuria - When blood glucose level exceeds the
  renal tubular maximum (Tm) of glucose (180
  mg/dL). Calories are lost in urine a compensatory
  hyperphagia. If the Hyperphagia does not keep
  pace with the glucosuria, loss of body fat ensues
  with clinical
• weight loss.

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Influence of feeding (High Insulin) or of
fasting (Low Insulin) on some Metabolic processes
in liver, muscles and adipose tissue.

• 3. Metabolic Acidosis- Insulinopenia, diminished
  energy production from glucose lipolysis.
  Peripheral utilization of fatty acids is
  incomplete and they are converted to ketone
  bodies in the liver. Accumulation of ketoacids
  (acetoacetic, ß-hydroxybutyric acids) will lead
  to metabolic acedosis. Ketoacidosis leads
  Kussmaul respiration (deep rapid breathing),
  fruity breath odor (acetone), diminished
  neurocognitive function, and possible coma.

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• 4. Dehydration and loss of electrolytes Ketones
  in association with cations are excreted in
  urine- loss of fluid and electrolytes, also
  hyperglycemia will lead to osmotic diuresis.

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• Hyperosmolality - It is due to dehydration and
  hyperglycemia.
• Serum osmolality in mOsm/kg2 (serum Na) glucose
  mg/ dL /18 BUN mg/ dL /3.

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• 6. Impaired level of consciousness- it is due to
  dehydration, hyperosmolality, metabolic acidosis,
  and diminished cerebral oxygen utilization.

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Clinical Manifestations
Different clinical presentations 1. The classic
presentation of diabetes in children is a history
of polyuria, polydipsia, hyperphagia, and loss of
weight (loss of body fat). The duration of these
symptoms is often less than 1 mo. Hyperphagia
occurs as a compensatory mechanism when calories
are lost in the urine (glucosuria).
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Clinical Manifestations

• 2. Enuresis (due to polyuria) in a previously
• toilet-trained child.
• 3. Insidious onset with lethargy, weakness,
• and weight loss (in spite of an increased
  Apetite).
• 4. Pyogenic skin infections or monolial
• vaginitis ( in teenage girls due to chronic
• glucosuria).

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Clinical Manifestations

• 5. Diabetic ketoacido sis- it is the clinical
  presentation of 20-40 of new-onset diabetic
  children and in children with known diabetes who
  omit insulin doses or who do not successfully
  manage the precipitating factors (trauma,
  infection, vomiting, and psychologic
  disturbances).

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Clinical Manifestations

• The early manifestations may be mild (nausea,
  vomiting, polyuria and dehydration).
• Kussmaul respiration (deep rapid respiration due
  to metabolic acidosis in an attempt to excrete
  excess CO2) with an odor of acetone on the breath
  (acetone is formed by non enzymatic conversion of
  acetoacetate).

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Clinical Manifestations

• Abdominal pain or rigidity (DD appendicitis,
  pancreatitis), nausea, and emesis.
• Severe dehydration
• Cerebral obtundation and ultimately coma.

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Diagnosis of T1DM

• Hyperglycemia- Non fasting blood glucose value
  exceeding 200 mg/ dL with typical symptoms.
• 2. Glucosuria

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DD

• The differential diagnosis of diabetes mellitus
  is not difficult, since this is virtually the
  only condition that gives rise to hyperglycemia,
  glucosuria and ketosis.
• . Renal glucosuria
• Isolated Congenital disorder.
• Renal tubular disorder (Fanconi syndrome, Renal
  disorders due to intoxication by heavy metals
  lead or outdated tetracycline or inborn errors
  of metabolism cystinosis).

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DD

• . Causes of metabolic acidosis
• Uremia, gastroenteritis with metabolic acidosis,
  hypoglycemia, lactic acidosis, salicylate
  intoxication, sepsis and encephalitis.
• . Physical stress
• Transient hyperglycemia with glucosuria, this is
  induced by counter regulatory hormones.

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New-Onset Diabetes without Ketoacidosis

• Excellent diabetes control involves many goals
• to maintain a balance between tight glucose
  control and avoiding hypoglycemia
• to eliminate polyuria and nocturia, to prevent
  ketoacidosis
• permit normal growth and development with
  minimal effect on lifestyle.
• initiation and adjustment of insulin,
• extensive teaching of the child and caretakers
• reestablishment of the life routines.

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• Each aspect should be addressed early in the
  overall care.
• therapy can begin in the outpatient setting,
  with complete team staffing by a pediatric
  endocrinologist, experienced nursing staff,
  dietitians with training as diabetes educators,
  and a social worker.
• Close contact between the diabetes team and
  family must be assured. Otherwise, initial
  therapy should be done in the hospital setting.

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Types of Insulin

• Rapid Acting
• Insulin lispro (Humalog)
• Insulin aspart (Novolog)
• Insulin glulisine (Apidra)
• Short-acting
• Regular
• Intermediate-acting
• NPH
• Long-acting
• Insulin glargine (Lantus)
• Insulin detemir (Levemir)

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Pharmacokinetics of Insulin Products

Rapid (lispro, aspart, glulisine)
Insulin Level
Short (regular)
Intermediate (NPH)
Long (glargine)
Long (detemir)
0 2 4 6 8 10 12 14
16 18 20 22 24
Hours
Adapted from Hirsch I. N Engl J Med.
2005352174-183.
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Normal Insulin Secretion
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Common Insulin Regimens

• The goal of treatment in type 1 DM is to provide
  insulin in as physiologic a manner as possible.
• Insulin replacement is accomplished by giving a
  basal insulin and a preprandial (premeal) insulin
• The basal insulin is either long-acting
  (glargine or detem
• The preprandial insulin is either rapid-acting
  (lispro, aspart, or glulisine) or short-acting
  (regular)

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• For patients on intensive insulin regimens
  (multiple daily injections or insulin pumps), the
  preprandial dose is based on the carbohydrate
  content of the meal (the carbohydrate ratio)
• plus a correction dose if their blood glucose
  level is elevated
• This method allows patients more flexibility in
  caloric intake and activity, but it requires
  more blood glucose monitoring and closer
  attention to the control of their diabetes.

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Basal/Bolus Treatment Program With Rapid-Acting
and Long-Acting Analogs
Rapid (lispro, aspart, glulisine)
Rapid (lispro, aspart, glulisine)
Rapid (lispro, aspart, glulisine)
Plasma insulin
Glargine or detemir
400
1600
2000
2400
400
800
1200
800
Breakfast
Lunch
Dinner
Bed
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Subcutaneous Insulin Dosing

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A four-step dosing schedule

• The basal insuline glargine should be 25-30 of
  the total dose in toddlers and 40-50 in older
  children. The remaining portion of the total
  daily dose is divided evenly as bolus injections
  for the three meals.

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Newly diagnosed children in the honeymoon may
only need 60-70 of a full replacement dose.
Total daily dose per kg increases with puberty.
Newly diagnosed children who do not use
carbohydrate dosing should divide the nonbasal
portion of the daily insulin dose into equal
doses for each meal
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• For example a 6 yr old child who weighs 20 kg
  needs about (0.7 U/kg/24 hr ? 20 kg) 14 U/24 hr
  with 7 U (50) as basal and 7 U as total daily
  bolus
• . Give basal as glargine at bedtime. Give 2 U
  lispro or aspart before each meal if the blood
  glucose is within target
• subtract 1 U if below target add 0.75 U for
  each 100 mg/dL above target (round the dose to
  the nearest 0.5 U). For finer control, extra
  insulin may be added in 50-mg/dL increments.

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• Indeed, bolus-basal treatment with multiple
  injections is better adapted to the physiologic
  profiles of insulin and glucose and can therefore
  provide better glycemic control than the
  conventional two-to-three dose regimen. This
  approach allows insulin doses to be changed as
  needed to correct hyperglycemia, supplement for
  additional anticipated carbohydrate intake, or
  subtract for exercise.

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• Some families may be unable to administer four
  daily injections. In these cases, a compromise
  may be needed
• A three-injection regimen Combining NPH with a
  rapid analog bolus at breakfast, a rapid acting
  analog bolus at supper, and NPH at bed time. This
  regimen may provide fair glucose control.
• A two-injection regimen This would require NPH
  combined with a rapid analog bolus at breakfast
  and supper. However, such a schedule would
  provide poor coverage for lunch and early
  morning, and would increase the risk of hypo
  glycemia at midmorning and early night.

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• a. The total daily insulin requirement is
  calculated.
• b. 2/3 of the daily dose is given before
  breakfast and 1/3 before supper (if the total
  dose is 30 U, 20 U will be given before breakfast
  and 10 U before supper).
• c. Each injection consists of intermediate and
  regular insulins in proportions of 2 1 or 31
  (20 U before breakfast 14U of NPH 6 U of
  regular insulin, and 10 U before supper 6 U of
  NPH 4 U of regular insulin).

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• Fine adjustment of insulin dose
• NPH in the morning dose has primary influence on
  before supper blood glucose (after about 12 hr).
• Morning regular insulin has primary influence on
  before lunch blood glucose (after about 6 hr).
• NPH in the evening dose has primary influence on
  breakfast blood glucose (after about 12 hr).
• Evening regular insulin has primary influence on
  before bed blood glucose (after about 6 hr).

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Fine Adjustment of the Two Injection Regimen

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• Examples
• Before lunch blood glucose level
• If the level is less than 80 mg/dL, decrease the
  dose of A.M regular insulin by 1-2 units.
• If the level is more than 150 mg/dL, increase the
  dose of A.M regular insulin by 1-2 units.
• Before supper blood glucose level
• If the level is less than 80 mg/dL, decrease the
  dose of A.M- NPH by 1-3 units.
• If the level is more than 150 mg/dl, increase the
  dose of A.M- NPH by 1-3 units and so on.

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Common insulin regimens include thefollowing

• Split or mixed NPH with rapid-acting (eg,
  lispro, aspart, or glulisine) or regular insulin
  before breakfast and supper
• Split or mixed variant NPH with rapid-acting or
  regular insulin before breakfast, rapid-acting or
  regular insulin before supper, and NPH before
  bedtime (the idea is to reduce fasting
  hypoglycemia by giving the NPH later in the
  evening)
• Continuous subcutaneous insulin infusion (CSII)
  Rapid-acting insulin infused continuously 24
  hours a day through an insulin pump at 1 or more
  basal rates, with additional boluses given before
  each meal and correction doses administered if
  blood glucose levels exceed target levels

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• The initial insulin schedule should be directed
  toward the optimal degree of glucose control in
  an attempt to duplicate the activity of the ß
  cell.
• There are inherent limits to our ability to
  mimic the ß cell. Exogenous insulin does not have
  a 1st pass to the liver, whereas 50 of
  pancreatic portal insulin is taken up by the
  liver, a key organ for the disposal of glucose
  absorption of an exogenous dose continues despite
  hypoglycemia, whereas endogenous insulin release
  ceases and serum levels quickly lower with a
  normally rapid clearance
• and absorption rate from an injection varies by
  injection site and patient activity level,
  whereas endogenous insulin is secreted directly
  into the portal circulation

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• Despite these fundamental physiologic
  differences, acceptable glucose control can be
  obtained with new insulin analogs used in a
  basal-bolus regimen, that is, with slow-onset,
  long-duration background insulin for between-meal
  glucose control and rapid-onset insulin at each
  meal.
• All preanalog insulins form hexamers, which must
  dissociate into monomers subcutaneously before
  being absorbed into the circulation.
• Thus, a detectable effect for regular (R)
  insulin is delayed by 30-60 min after injection.
  This, in turn, requires delaying the meal
  30-60 min after the injection for optimal
  effecta delay rarely attained in a busy child's
  life

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• R has a wide peak and a long tail for bolus
  insulin (Figs. 583-6 and 583-7). This profile
  limits postprandial glucose control, produces
  prolonged peaks with excessive hypoglycemic
  effects between meals, and increases the risk of
  nighttime hypoglycemia. These unwanted
  between-meal effects often necessitate feeding
  the insulin with snacks and limiting the overall
  degree of blood glucose control.

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• NPH and Lente insulins also have inherent limits
  because they do not create a peakless background
  insulin level (see Fig. 583-7C-E). This produces
  significant hypoglycemic effect during the
  midrange of their duration. Thus, it is often
  difficult to predict their interaction with
  fast-acting insulins. When R is combined with NPH
  or Lente (see Fig. 583-7E), the composite insulin
  profile poorly mimics normal endogenous insulin
  secretion. There are broad areas of excessive
  insulin effect alternating with insufficient
  effect throughout the day and night. Lente and
  Ultralente insulins have been discontinued and
  are no longer available.

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• Frequent blood glucose monitoring and insulin
  adjustment are necessary in the 1st weeks as the
  child returns to routine activities and adapts to
  a new nutritional schedule, and as the total
  daily insulin requirements are determined.
• The major physiologic limit to tight control is
  hypoglycemia. Intensive control dramatically
  reduces the risk of long-term vascular
  complications it is associated with a 3-fold
  increase in severe hypoglycemia.
• Use of insulin analogs moderates but does not
  eliminate this problem.
• Some families may be unable to administer 4 daily
  injections.
• In these cases, a compromise may be needed.
• A 3-injection regimen combining NPH with a rapid
  analog bolus at breakfast, a rapid-acting analog
  bolus at supper, and NPH at bedtime may provide
  fair glucose control

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• Further compromise to a 2-injection regimen (NPH
  and rapid analog at breakfast and supper) may
  occasionally be needed. However, such a schedule
  would provide poor coverage for lunch and early
  morning, and would increase the risk of
  hypoglycemia at midmorning and early night.

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Insulin Therapy

• Several factors influence the initial daily
  insulin dose per kilogram of body weight.
• The dose is usually higher in pubertal children.
• most children with new-onset diabetes have some
  residual ß-cell function (the honeymoon period),
  which reduces exogenous insulin needs
• Children with long-standing diabetes and no
  insulin reserve require about 0.7 U/kg/day if
  prepubertal
• 1.0 U/kg/day at midpuberty,
• 1.2 U/kg/day by the end of puberty.
• The optimal insulin dose can only be determined
  empirically, with frequent self-monitored blood
  glucose levels and insulin adjustment by the
  diabetes team
• Residual ß-cell function usually fades within a
  few months and is reflected as a steady increase
  in insulin requirements and wider glucose
  excursions.

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INSULIN DOSAGE
Insulin requirement is based upon the body
weight, age, and pubertal stage of the child In
general, the newly diagnosed child requires an
initial total daily insulin dose of 0.5 to 1.0
units/kg. Prepubertal children usually require
lower doses, and the dose requirement may be as
low as 0.25 units/kg for a variable period
following diagnosis. Higher doses are needed in
pubertal children, patients in ketoacidosis, or
in patients receiving glucocorticoid therapy.
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INSULIN DOSAGE
In infants and toddlers who receive their insulin
by syringe, the insulin dose may be so small that
dilution is required to allow for easier and more
precise administration. The smallest dose of
insulin that can be accurately administered
without dilution using a syringe is 0.5
units. Many insulins can be diluted either at a
specialized pharmacy or at home with proper
training. Specific diluent for many insulin
preparations is available from the insulin
manufacturer. Some insulin pumps can deliver
much smaller doses of insulin, of the order of
0.025 units at a time, often obviating this
problem.
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INSULIN DOSAGE

• On average, 1 unit of insulin is required to
  cover
• 20 grams of carbohydrates in most young children
  (1 to 6 years of age)
• 10 to 12 grams of carbohydrates in older
  prepubertal children
• 8 to 10 grams in pubertal adolescents

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INSULIN DOSAGE
When converting a patient from MDI or
conventional therapy to insulin pump, the initial
dose is dependent on diabetes control and total
daily insulin dose. If control has been
excellent, the initial daily insulin pump dose is
10 to 20 percent less than the previous dose . If
control has been poor, the same total previous
daily dose should be used. One study suggests
patients using detemir insulin may require
greater dose reductions (26 to 33 percent) when
switching from MDI to the insulin pump .
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Glycemic TargetsGlucose values are plasma
(mg/mL)
Age Pre-Meal BG HS/Night BG HbA1c
Toddler (0-5 yrs) 100-180 110-200 7.5 8.5
School-age (6-11 yrs) 90-180 100-180 lt8
Adolescent (12-19 yrs) 90-130 90-150 lt7.5 Adults lt7
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• Insulin is sensitive to heat and exposure to
  oxygen. Once a bottle of insulin is open, it
  should be used for no more than 28 days and then
  discarded even if there is still some insulin in
  the bottle, it may have lost its clinical
  effectiveness.
• Insulin kept in a pump reservoir for longer than
  3 days may lose its clinical effectiveness
  (though insulin aspart has now been approved for
  use for as long as 6 days in a pump).
• Sometimes, insulin distributed from the pharmacy
  has been exposed to heat or other environmental
  factors and therefore may be less active.
• If a patient is experiencing unexplained high
  blood sugar levels, new insulin vials should be
  opened and used.

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Insulin absorption ? Insulin activity profiles
show substantial variability both day to day in
the same individuals and between individuals,
particularly children. ? The onset, peak effect
and duration of action depend upon many factors
which significantly affect the speed and
consistency of absorption. ? Young people and
care providers should know the factors which
influence insulin absorption such as Age
(young children, less subcutaneous
fat?faster absorption) . Fat mass (large
subcutaneous fat thickness , lipohypertrophy,
also with rapid-acting analogs ?slower
absorption).
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Regular insulin (short acting) Regular soluble
insulin (usually identical to human insulin) is
still used as an essential component of most
daily replacement regimens in many parts of the
world either combined with ? Intermediate-acting
insulin in twice daily regimen. ? As pre-meal
bolus injections in basal-bolus regimens (given
2030 min before meals) together with
intermediate-acting insulin twice daily or a
basal analog given once or twice daily.
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Intermediate acting insulins The action profiles
of these insulinsmake them suitable for twice
daily regimens and for pre-bed dosage in
basal-bolus regimens Two principal preparations
exist ? Isophane NPH (neutral protamine
Hagedorn) insulins. ? Crystalline zinc acetate
insulin (insulin zinc suspensions, IZS or lente
insulins). Isophane insulins are mostly used in
children, mainly because of their suitability for
mixing with regular insulin in the same syringe,
vial or cartridge without interaction. Lente
insulins are discontinued in many countries. NOTE
When regular insulin is mixed with lente
preparations it reacts with excess zinc, blunting
its short acting properties .
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Regular Insulin are best suited for IV therapy
and are used in the following crisis
situations Diabetic ketoacidosis. Control of
diabetes during surgical procedures. Rapid-acting
analog insulin can also be given IV . However,
the effect is not superior to that of regular
insulin and it is more expensive.
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Insulin concentrations ? The most widely
available insulin concentration is 100 IU/ml (U
100). ? Treatment with U 40 (40 IU/ml), U50 or
other concentrations such as U500 is also
acceptable, subject to availability and special
needs. ? Care must be taken to ensure that the
same concentration is supplied each time new
supplies are received. ? Very young children
occasionally require insulin diluted with diluent
obtained from the manufacturer, but special care
is needed in dilution and drawing up the insulin
into the syringe. Rapid acting insulin can be
diluted to U10 or U50 with sterile NPH diluent
and stored for 1 month for use in pumps for
infants or very young children.
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Basal/Bolus Treatment Program With Rapid-Acting
and Long-Acting Analogs
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HbA1c Statistics for CHLA 2003 Type 1 Diabetes gt
1 year, followed gt 1 yearEnrolled in Long-term
study total n 1800
n Average SD
All patients 1181 8.2 1.6
Males 579 8.2 1.6
Females 602 8.2 1.6
lt 5 51 7.8 1.3
5-10 355 7.9 1.3
11-16 489 8.4 1.8
17-19 gt20 157 127 8.3 1.5 7.4 1.3
95
PenFill Cartridges or NovoLog (insulin aspart
rdna origin inj) FlexPen Prefilled syringe.
Keep at room temperature below 86F (30C) for
up to 28 days. Do not store a PenFill cartridge
or NovoLog (insulin aspart rdna origin inj)
FlexPen Prefilled syringe that you are using in
the refrigerator. Keep PenFill cartridges and
NovoLog (insulin aspart rdna origin inj)
FlexPen Prefilled syringe away from direct heat
or light. Throw away a used PenFill cartridge or
NovoLog (insulin aspart rdna origin inj)
FlexPen Prefilled syringes after 28 days, even if
there is insulin left in the cartridge or syringe.
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Monitoring

• Success in the daily management of the diabetic
  child can be measured by the competence acquired
  by the family, and subsequently by the child, in
  assuming responsibility for daily diabetic
  care. Their initial and ongoing instruction in
  conjunction with their supervised experience can
  lead to a sense of confidence in making
  intermittent adjustments in insulin dosage for
  dietary deviations, for unusual physical activity
• and even for some minor intercurrent illnesses,
  as well as for otherwise unexplained repeated
  hypoglycemic reactions and excessive glycosuria.
  Such acceptance of responsibility should make
  them relatively independent of the physician for
  their ordinary care. The physician must maintain
  ongoing interested supervision and shared
  responsibility with the family and the child.

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• Self-monitoring of blood glucose (SMBG) is an
  essential component of managing diabetes.
  Monitoring often also needs to include insulin
  dose, unusual physical activity, dietary changes,
  hypoglycemia, intercurrent illness, and other
  items that may influence the blood glucose.
• These items may be valuable in interpreting the
  SMBG record, prescribing appropriate adjustments
  in insulin doses, and teaching the family. If
  there are discrepancies in the SMBG and other
  measures of glycemic control (such as the HbA1c),
  the clinician should attempt to clarify the
  situation in a manner that does not undermine
  their mutual confidence

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• Daily blood glucose monitoring has been markedly
  enhanced by the availability of strips
  impregnated with glucose oxidase that permit
  blood glucose measurement from a drop of blood.
• A portable calibrated reflectance meter can
  approximate the blood glucose concentration
  accurately. Many meters contain a memory chip
  enabling recall of each measurement, its average
  over a given interval, and the ability to display
  the pattern on a computer screen
• . Such information is a useful educational tool
  for verifying degree of control and modifying
  recommended regimens.
• A small, spring-loaded device that automates
  capillary bloodletting (lancing device) in a
  relatively painless fashion is commercially
  available.

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• Parents and patients should be taught to use
  these devices and measure blood glucose at least
  4 times dailybefore breakfast, lunch, and supper
  and at bedtime. When insulin therapy is initiated
  and when adjustments are made that may affect the
  overnight glucose levels,
• SMBG should also be performed at 12 a.m. and 3
  a.m. to detect nocturnal hypoglycemia. Ideally,
  the blood glucose concentration should range from
  approximately 80 mg/dL in the fasting state to
  140 mg/dL after meals. In practice, however, a
  range of 60-220 mg/dL is acceptable
• based on age of the patient (Blood glucose
  measurements that are consistently at or outside
  these limits, in the absence of an identifiable
  cause such as exercise or dietary indiscretion,
  are an indication for a change in the insulin
  dose.

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• If the fasting blood glucose is high, the
  evening dose of long-acting insulin is increased
  by 10-15 and/or additional fast-acting insulin
  (lispro or aspart) coverage for bedtime snack may
  be considered.
• If the noon glucose level exceeds set limits,
  the morning fast-acting insulin (lispro or
  aspart) is increased by 10-15
• If the pre-supper glucose is high, the noon dose
  of fast-acting insulin is increased by 10-15.
• If the pre-bedtime glucose is high, the
  pre-supper dose of fast-acting insulin is
  increased by 10-15.
• Similarly, reductions in the insulin type and
  dose should be made if the corresponding blood
  glucose measurements are consistently below
  desirable limits.

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Hypoglycemic Reactions

• Hypoglycemia is the major limitation to tight
  control of glucose levels. Once injected, insulin
  absorption and action are independent of the
  glucose level, thus creating a unique risk of
  hypoglycemia from an unbalanced insulin effect.
  Insulin analogs may help reduce but cannot
  eliminate this risk.
• Most children with T1DM can expect mild
  hypoglycemia each week, moderate hypoglycemia a
  few times each year, and severe hypoglycemia
  every few years. These episodes are usually not
  predictable,
• although exercise, delayed meals or snacks, and
  wide swings in glucose levels increase the risk.

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Infants and toddlers are at higher risk because
they have more variable meals and activity
levels, are unable to recognize early signs of
hypoglycemia, and are limited in their ability to
seek a source of oral glucose to reverse the
hypoglycemia. The very young have an increased
risk of permanently reduced cognitive function as
a long-term sequela of severe hypoglycemia. For
this reason, a more relaxed degree of glucose
control is necessary until the child matures
Hypoglycemia can occur at any time of day or
night.
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• Early symptoms and signs (mild hypoglycemia) may
  occur with a sudden
• decrease in blood glucose to levels that do not
  meet standard criteria
• For hypoglycemia in nondiabetic children.
• The child may show pallor, sweating, apprehension
  or fussiness, hunger,
• tremor, and tachycardia, all due to the surge in
  catecholamines as the
• body attempts to counter the excessive insulin
  effect. Behavioral
• changes such as tearfulness, irritability,
  aggression, and naughtiness are
• more prevalent in children.

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• As glucose levels decline further, cerebral
  glucopenia occurs with drowsiness,
• personality changes, mental confusion, and
  impaired judgment (moderate
• hypoglycemia) progressing to inability to seek
  help and seizures or coma
• (severe hypoglycemia). Prolonged severe
  hypoglycemia can result in a
• depressed sensorium or Stroke like focal motor
  deficits that persist after the
• hypoglycemia has resolved.
• Although permanent sequelae are rare, severe
  hypoglycemia is frightening for
• the child and family and can result in
  significant reluctance to attempt even
• Moderate glycemic control afterward.

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• Important counter-regulatory hormones in children
  include growth hormone, cortisol, epinephrine,
  and glucagon. The latter 2 seem more critical in
  the older child.
• Many older patients with long-standing T1DM lose
  their ability to secrete glucagon in response to
  hypoglycemia.
• In the young adult, epinephrine deficiency may
  also develop as part of a general autonomic
  neuropathy. This substantially increases the risk
  of hypoglycemia because the early warning signals
  of a declining glucose level are due to
  catecholamine release.

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• Recurrent hypoglycemic episodes associated with
  tight metabolic control may aggravate partial
  counter-regulatory deficiencies, producing a
  syndrome of hypoglycemia unawareness and reduced
  ability to restore euglycemia (hypoglycemia-associ
  ated autonomic failure). Avoidance of
  hypoglycemia allows some recovery from this
  unawareness syndrome

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• The most important factors in the management of
  hypoglycemia are an understanding by the patient
  and family of the symptoms and signs of the
  reaction and an anticipation of known
  precipitating factors such as gym or sports
  activities. Tighter glucose control increases the
  risk.
• Families should be taught to look for typical
  hypoglycemic scenarios or patterns in the home
  blood glucose log, so that they may adjust the
  insulin dose and avert predictable episodes.
• A source of emergency glucose should be available
  at all times and places, including at school and
  during visits to friends. If possible, it is
  initially important to document the hypoglycemia
  before treating, because some symptoms may not
  always be due to hypoglycemia.
• Most families and children develop a good sense
  for true hypoglycemic episodes and can institute
  treatment before testing. Any child suspected of
  having a moderate to severe hypoglycemic episode
  should also be treated before testing.

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• It is important not to give too much glucose
  5-10 g should be given as juice or a
  sugar-containing carbonated beverage or candy,
  and the blood glucose checked 15-20 minutes
  later. Patients, parents, and teachers should
  also be instructed in the administration of
  glucagon when the child cannot take glucose
  orally.
• An injection kit should be kept at home and
  school. The intramuscular dose is 0.5 mg if the
  child weighs less than 20 kg and 1.0 mg if more
  than 20 kg. This produces a brief release of
  glucose from the liver. Glucagon often causes
  emesis, which precludes giving oral
  supplementation if the blood glucose declines
  after the glucagon effects have waned. Caretakers
  must then be prepared to take the child to the
  hospital for IV glucose administration,

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Dawn Phenomenon

• There are several reasons that blood glucose
  levels increase in the early morning hours before
  breakfast. The most common is a simple decline in
  insulin levels and is seen in many children using
  NPH or Lente as the basal insulin at supper or
  bedtime. This usually results in routinely
  elevated morning glucose.
• The thought to be due mainly to overnight growth
  hormone secretion and increased insulin
  clearance. It is a normal physiologic process
  seen in most nondiabetic adolescents, who
  compensate with more insulin output. A child with
  T1DM cannot compensate and may actually have
  declining insulin levels if using evening NPH or
  Lente. The dawn phenomenon is usually recurrent
  and modestly elevates most morning glucose levels.

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Somogyi phenomenon

• Rarely, high morning glucose is due to the
  Somogyi phenomenon, a theoretical rebound from
  late night or early morning hypoglycemia, thought
  to be due to an exaggerated counter-regulatory
  response.
• It is unlikely to be a common cause, in that
  most children remain hypoglycemic (do not
  rebound) once nighttime glucose levels decline.
  Continuous glucose monitoring systems may help
  clarify ambiguously elevated morning glucose
  levels.

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Brittle Diabetes

• The term has been used to describe the child,
  usually an adolescent female, with unexplained
  wide fluctuations in blood glucose, often with
  recurrent DKA, who is taking large doses of
  insulin.
• An inherent physiologic abnormality is rarely
  present because these children usually show
  normal insulin responsiveness when in the
  hospital environment.
• Psychosocial or psychiatric problems, including
  eating disorders, and dysfunctional family
  dynamics are usually present, which preclude
  effective diabetes therapy
• . Hospitalization is usually needed to confirm
  the environmental effect, and aggressive
  psychosocial or psychiatric evaluation is
  essential. Therefore, clinicians should refrain
  from using brittle diabetes as a diagnostic
  term.

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Management During Infections

• Although infections are no more common in
  diabetic children than in nondiabetic ones, they
  can often disrupt glucose control and may
  precipitate DKA.
• In addition, the diabetic child is at increased
  risk of dehydration if hyperglycemia causes an
  osmotic diuresis or if ketosis causes emesis.
• Counter-regulatory hormones associated with
  stress blunt insulin action and elevate glucose
  levels. If anorexia occurs, however, lack of
  caloric intake increases the risk of
  hypoglycemia.
• Although children younger than 3 yr tend to
  become hypoglycemic and older children tend
  toward hyperglycemia, the overall effect is
  unpredictable. Therefore, frequent blood glucose
  monitoring and adjustment of insulin doses are
  essential elements of sick day guidelines

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• The overall goals are to maintain hydration,
  control glucose levels, and avoid ketoacidosis.
• This can usually be done at home if proper sick
  day guidelines are followed and with telephone
  contact with health care providers. The family
  should seek advice if home treatment does not
  control ketonuria, hyperglycemia, or
  hypoglycemia, or if the child shows signs of
  dehydration.
• A child with large ketonuria and emesis should
  be seen in the emergency department for a general
  examination, to evaluate hydration, and to
  determine whether ketoacidosis is present by
  checking serum electrolytes, glucose, pH, and
  total CO2.
• A child whose blood glucose declines to less than
  50-60 mg/dL (2.8-3.3 mmol/L) and who cannot
  maintain oral intake may need IV glucose,
  especially if further insulin is needed to
  control ketonemia.

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Management During Surgery

• Surgery can disrupt glucose control in the same
  way as can intercurrent infections. Stress
  hormones associated with the underlying condition
  as well as with surgery itself decrease insulin
  sensitivity.
• This increases glucose levels, exacerbates fluid
  losses, and may initiate DKA. On the other hand,
  caloric intake is usually restricted, which
  decreases glucose levels. The net effect is as
  difficult to predict as during an infection.
• Vigilant monitoring and frequent insulin
  adjustments are required to maintain euglycemia
  and avoid ketosis.

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• Maintaining glucose control and avoiding DKA are
  best accomplished with IV insulin and fluids. A
  simple insulin adjustment scale based on the
  patient's weight and blood glucose level can be
  used in most situations
• The IV insulin is continued after surgery as the
  child begins to take oral fluids the IV fluids
  can be steadily decreased as oral intake
  increases. When full oral intake is achieved, the
  IV may be capped and subcutaneous insulin begun.
  When surgery is elective, it is best performed
  early in the day, allowing the patient maximal
  recovery time to restart oral intake and
  subcutaneous insulin therapy.

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• When elective surgery is brief (less than 1 hr)
  and full oral intake is expected shortly
  afterward, one may simply monitor the blood
  glucose hourly and give a dose of insulin analog
  according to the child's home glucose correction
  scale.
• If glargine or detemir is used as the basal
  insulin, a full dose is given the evening before
  planned surgery. If NPH or Lente is used, one
  half of the morning dose is given before surgery.
  The child should not be discharged until blood
  glucose levels are stable and oral intake is
  tolerated.

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Thank you!!!