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DIABETES MELLITUS TYPE 1 & MANAGEMENT OF DIABETIC KETOACIDOSIS
1. DIABETES MELLITUSDIABETES MELLITUS
TYPE 1 &TYPE 1 &
MANAGEMENT OFMANAGEMENT OF
DIABETICDIABETIC
KETOACIDOSISKETOACIDOSIS
PRESENTED BY
DR ASHISH SHARMA
GUIDED BY
DR MEENA PATEL
2. DEFINITION
Metabolic disorder of multiple
etiologies characterized by chronic
hyperglycemia with disturbances of
carbohydrate, fat and protein
metabolism resulting from defects of
insulin secretion, insulin action or
both.
3. OLD CLASSIFICATION
(1985)
Type 1, Insulin-dependent (IDDM)
Type 2, Non Insulin-dependent (NIDDM)
– obese
– non-obese
– MODY
IGT
Gestational Diabetes
4. WHO CLASSIFICATION
2000
Is based on etiology not on type of
treatment or age of the patient.
Type 1 Diabetes
(idiopathic or autoimmune β-cell destruction)
Type 2 Diabetes
(defects in insulin secretion or action)
Other specific types
5. Both type 1 & type 2 can be further subdivided
into:
Not insulin requiring
Insulin requiring for control
Insulin requiring for survival
6. Type 1 Diabetes
Mellitus
Formerly called insulin-dependent
diabetes mellitus (IDDM) or juvenile
diabetes
T1DM is characterized by low or absent levels of
endogenously produced insulin
7. EPIDEMIOLOGY
• The onset occurs predominantly in
childhood, with median age of 7-15 yr,
but it may present at any age.
• Indian data suggest an incidence of
10.5/100,000/yr .
• India would have 79 million diabetes by
2030, the highest for any country in the
world.
8. Pathogenesis & Natural
history
The natural history includes
distinct stages
1) Initiation of autoimmunity
2)Preclinical autoimmunity with progressive
loss of β-cell function
3)Onset of clinical disease
4)Transient remission( “Honeymoon period”)
5)Established disease
6)Development of complications
9. Both genetic ,environmental and autoimmune
factors contribute to the pathogenesis.
Genetic factors-
Genetic susceptibility to T1DM is determined
by several genes .
HLA complex accounts for almost 50 % of
genetic risk for type 1 diabetes.
Some of the known associations include the
HLA DR3/4-DQ2/8 genotype
10. Association with DR3 has been reported in
Indians.
Risk of diabetes is also increased when a
parent has diabetes and this risk differs
between the 2 parents; the risk is 2% if the
mother has diabetes, but 7% when the
father has diabetes.
In monozygotic twins, the concordance
rate ranges from 30-65%, whereas
dizygotic twins have a concordance rate of
6-10%.
11. Envoirmental factors
Many envoirmental agents are thought to
trigger the development of type 1 diabetes
including,
Viral infections- Enterovirus , mumps ,
rubella
Diet- Breast-feeding may lower the risk of
T1DM.
Early introduction of cow's milk protein
and early exposure to gluten have both
been implicated in the development of
autoimmunity
12. Autoimmune factors
Whatever the triggering factor, it seems that
in most cases of T1DM that are diagnosed in
childhood.
The 1st signs of autoimmunity appear before
age 2 yr.
Insulin associated antibodies (IAA)
↓
Glutamic acid decarboxylase 65 kd (GAD65)
&
tyrosine phosphatase insulinoma-associated
13. . The earliest antibodies are predominantly
of the IgG1 subclass
The appearance of autoimmunity is followed
by progressive destruction of β cells.
Antibodies are a marker for the presence of
autoimmunity, but the actual damage to the β
cells is primarily T-cell mediated
14.
15.
16. Pathophysiology
Insulin performs a critical role in the storage
and retrieval of cellular fuel.
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
17. Pathophysiology….
T1DM is a progressive low-insulin catabolic
state in which feeding does not reverse but
rather exaggerates these catabolic processes.
At even lower insulin levels, the liver
produces excessive glucose via glycogenolysis
and gluconeogenesis, and fasting
hyperglycemia begins.
18. 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)
19. Pathophysiology….
These hormones, in turn, contribute to the
metabolic decompensation by promoting
glycogenolysis, gluconeogenesis, lipolysis,
and ketogenesis (glucagon, epinephrine,
growth hormone, and cortisol) while
decreasing glucose utilization and glucose
clearance.
22. DIAGNOSIS
In symptomatic children a random
plasma glucose >11.1 mmol
(200 mg) is diagnostic.
A modified OGTT (fasting & 2h) may
be needed in asymptomatic children
with hyperglycemia if the cause is not
obvious.
Remember: acute infections in young
non-diabetic children can cause
hyperglycemia without ketoacidosis.
24. TREATMENT GOALS
Prevent death & alleviate symptoms
Achieve biochemical control
Maintain growth & development
Prevent acute complications
Prevent or delay late-onset complications
25. TREATMENT
ELEMENTS
Education
Insulin therapy
Diet and meal planning
Monitoring
HbA1c every 2-months
Home regular BG monitoring
Home urine ketones tests when indicated
26. EDUCATION
Educate child & care givers
about:
Diabetes
Insulin
Life-saving skills
Recognition of Hypo & DKA
Meal plan
Sick-day management
27. INSULIN
A polypeptide made of 2 β-chains.
Discovered by Bants & Best in 1921.
Animal types (porcine & bovine) were used
before the introduction of human-like insulin
(DNA-recombinant types).
Recently more potent insulin analogs are
produced by changing aminoacid sequence.
28. FUNCTION OF
INSULIN
Insulin being an anabolic hormone
stimulates protein & fatty acids
synthesis.
Insulin decreases blood sugar
1. By inhibiting hepatic glycogenolysis and
gluconeogenesis.
2. By stimulating glucose uptake, utilization
& storage by the liver, muscles &
adipose tissue.
29. Characteristics of
Insulin
There are three characteristics of insulin:
Onset- Is the length of time before
insulin reaches the bloodstream and
begins lowering blood glucose.
Peaktime- Is the time during which
insulin is at maximum strength in terms
of lowering blood
glucose.
Duration- Is how insulin continues to
lower blood glucose.
30. The Basics of Insulin:
4 Types
Rapid-acting insulin
Regular or short-acting insulin
Intermediate-acting insulin
Long-acting insulin
31. Rapid-acting Insulin
Examples: insulin lispro or insulin aspart
Onset: Begins to work at about 5
minutes
Peaktime: Peak is about 1 hour
Duration: Continues to work for about 2-
4 hours
32. Regular or Short-
acting Insulin
Examples: insulin lispro, Aspart
Onset: Reaches the bloodstream within
30 minutes after injection.
Peaktime: Peaks anywhere from 2-3
hours after injection.
Duration: Effective for approximately 3-6
hours.
34. Long-acting Insulin
Examples: insulin glargine
Onset: Reaches the bloodstream 6-
10 hours after injection
Duration: Usually effective for 20-24
hours
35. INSULIN
CONCENTRATIONS
Insulin is available in different concentrations
40, 80 & 100 Unit/ml.
WHO now recommends U 100 to be the only
used insulin to prevent confusion.
Special preparation for infusion pumps is
soluble insulin 500 U/ml.
36. Insulin Pump Therapy
Continuous subcutaneous insulin infusion
(CSII) via battery-powered pumps provides a
closer approximation of normal plasma
insulin profiles.
It accurately deliver a small baseline
continuous infusion of insulin, coupled with
parameters for bolus therapy.
The bolus insulin determined by amount of
carbohydrate intake and blood sugar level
37.
38. INSULIN REGIMENS
Twice daily: either NPH alone or
NPH+SI.
Thrice daily: SI before each meal and
NPH only before dinner.
Intensive 4 times/day: SI before meals
+ NPH or Glargine at bed time.
Continuous s/c infusion using pumps
loaded with SI.
39. NEW INSULIN
PREPARATIONS
Inhaled insulin proved to be effective &
will be available within 2 years.
Nasal insulin was not successful
because of variable nasal absorption.
Oral insulin preparations are under
trials.
41. PRACTICAL
PROBLEMS
Non-availability of insulin in poor countries
injection sites & technique
Insulin storage & transfer
Mixing insulin preparations
Insulin & school hours
Adjusting insulin dose at home
Sick-day management
Recognition & Rx of hypo at home
42. DIET REGULATION
Regular meal plans with calorie exchange
options are encouraged.
50-60% of required energy to be obtained
from complex carbohydrates.
Distribute carbohydrate load evenly during
the day preferably 3 meals & 2 snacks with
avoidance of simple sugars.
Encouraged low salt, low saturated fats and
high fiber diet.
43. EXERCISE
Decreases insulin requirement in
diabetic subjects by increasing both
sensitivity of muscle cells to insulin &
glucose utilization.
It can precipitate hypoglycemia in the
unprepared diabetic patient.
It may worsen pre-existing diabetic
retinopathy.
44. MONITORING
Compliance (check records)
HBG tests
HbA1 every 2 months
Insulin & meal plan
Growth & development
Well being & life style
School & hobbies
45. ADVANCES IN
MONITORING
Smaller & accurate meters for intermittent
BG monitoring
Glucowatch continuous monitoring using
reverse iontophoresis to measure
interstitial fluid glucose every 20 minutes
Glucosensor that measures s/c capillary
BG every 5 minutes
Implantable sensor with high & low BG
alarm
46. ADVANCES IN
MANAGEMENT
Better understanding of diabetes allows
more rational approach to therapy.
Primary prevention could be possible if
the triggering factors are identified.
The DCCT studies proves beyond doubt
that chronic diabetic complication can be
controlled or prevented by strict glycemic
control.
47. TREATMENT MADE
EASY
Insulin pens & new delivery products
Handy insulin pumps
Fine micro needles
Simple accurate glucometers
Free educational material
Computer programs for comprehensive
management & monitoring
48. TELECARE SYSTEMS
IT has improved diabetes care
Internet sites for education & support
Web-based systems for telecare are
now available. The patient feeds his
HBGM data and get the physician,
nurse & dietician advice on the
required modification to diet & insulin
treatment.
49. PITFALLS OF
MANAGEMENT
Delayed diagnosis of IDDM
The honey-moon period
Detection & treatment of NIDDY
Problems with diagnosis & treatment of
DKA & hypoglycemia
Somogyi’s effect & dawn phenomenon
may go unrecognized.
50. FUTURE PROMISES
The cure for IDDM is successful islet cell
transplantation, which will be available in the
near future.
Primary prevention by a vaccine or drug will
be offered to at risk subjects identified by
genetic studies.
Gene modulation therapy for susceptible
subjects is a promising preventive measure.
51. Pancreas & Islet Cell
Transplantation
Pancreas transplants are usually given
to diabetics with end stage renal
disease.
Islet cell transplants, the ultimate
treatment of type 1 diabetes is under
trial in many centers in the US &
Europe with encouraging results but
graft rejection & recurrence of
autoimmunity are serious limitations.
52. IMMUNE MODULATION
Immunosuppressive therapy for
Newly diagnosed
Prolonged the honey moon
For high risk children
Immune modulating drugs
Nicotinamide
mycophenolate
53. GENE THERAPY
Blocks the immunologic attack against
islet-cells by DNA-plasmids encoding
self antigen.
Gene encode cytokine inhibitors.
Modifying gene expressed islet-cell
antigens like GAD.
55. PREVENTION OF
DIABETES
Primary prevention
• Identification of diabetes gene
• Tampering with the immune system
• Elimination of environmental factor
Secondary prevention
• Immunosuppressive therapy
Tertiary prevention
• Tight metabolic control & good monitoring
57. .
INTRODUCTION
DKA,a life threatning complication of
diabetes mellitus,occurs more commonly
in children with type 1 DM than type 2
DM.
Hyperglycemia,metabolic acidosis,
ketonemia,dehydration and vaious
electolyte abnormalities result from a
relative and absolute deficiency of insulin
with or without excess of counter
regulatory hormones
58. .
Definition
DKA in children is defined as
hypgerglycemia(serum glucose conc.
>200-300mg/dl) in the presence of
metabolic acidosis (blood pH<7.3 with
serum bicarbonate level<15 mEq/L) and
ketonemia(presence of ketones in blood).
When measured sr ketones (b hydroxy
butyrate plus acetoacetate)exceed 31 mg/dl
with or without ketonuria >80mg/dl
59. .
CLINICAL HISTORY
Polyuria
Polydipsia
Weight loss
Nausea,vomiting,abdominal pain
Headache
Restlessness,irritability
Lethargy,altered sensorium,loss of
conciousness
Fever
65. .
Resuscitation
Airway+NG tube
Circulation(10-20ml/kg of 0.9%
NS over 30-60 mins)
Repeat if necessary- initial
expansion should not exceed
total 30 ml/kg
Intravenous therapy
Calculate fluid requirments
(maintainence + deficit)
Correct over 24 hrs with 0.9NS
for first 8-12 hrs followed by
0.45%NS(Add KCl 40 mEq/L)
Start insulin infusion 0.1 u/kg/hr
ECG for hypo/hyperkalemic
changes
Start with
subcutaneous insulin
0.25U/kg 3-4hrly
No improvement
66. .
Monitoring
•Hourly blood glucose
•Neurological status
atleast hourly
•Hourly fluid input
output
•Electrolytes and then
4hrly
•Blood gas at
admission and then as
indicated
•Monitor ECG for hypo
and hyperkalemic
changes
No
improvement
Reevaluate
•Uncorrected
hypovolemia
•Review dose and
rate of insulin
infusion
•Neurological
deterioration
warning signs
•Headache
•Irritability
•Slowing heart rate
•Reduced
conciousness level
•Hypertension
•Bradycardia
•Pupillary inequality
Consider
Cerebral
Edema(Exclude
Hypoglycemia)
67. .
Intravenous therapy
•Consider fluid to 0.45 NS +dextrose 5%
•Continue monitoring as above
•Consider reducing Insulin 0.05 U/kg/hr when
>pH.7.3,blood glucose <250 mg% and dextrose
containing fluid has been started,
Improvement
•No emesis
•Normal electrolytes
•CO2 >16mEq/L
•pH>7.3
Insulin
Start
subcutaneius
insulin and then
stop iv insulin
infusion 1 hr
later
68. DIABETIC KETOACIDOSIS
TREATMENT PROTOCOL.
1ST
hr 10-20 ml/kg IV bolus 0.9% NaCl or
LR
Insulin drip at 0.05 to 0.10 u/kg/hr
Quick volume expansion;may be
repeated.NPO.Monitor I/O,neurologic
status.Usefloe sheet. Have Mannitol a
bedside;1 g/kg IV push for cerebral
edema
2nd
hr until DKA
resolution
0.45%NaCl:plus continue Insulin
drip
20 mEq/l Kphos and 20 mEq/l
Kac.5% glucose if blood sugar <250
mg/dl
IV rate= 85 ml/kg+maintainence-
bolus/23hr
If K<3mEq/L,give 0.5 to 1 mEq/kg as or
K solution OR increase IV K to 80 mEq/
Variable Oral intake with subcutaneous
insulin
No emesis;CO2> 16 mEq/L;normal
electrolytes
TIME THERAPY COMMENTS
69. .
• Note that initial IV bolus is considered as
part of the total fluid allowed in the 1st
24
hr and is sutracted before calculating the
IV rate.
• Sample calculation for a 30 kg child:
• 1st
hr=300ml IV bolus 0.9%NaCl or LR
• 2nd
and subsequent hrs=(85x30)+1750-
300/23=175 ml/hr
• (0.45%NaCl with 20 mEq/L Kphos and 20
mEq/L Kac)
70. .
• The Milwaukee protocol can be used for
children of all ages and with all degree of
DKA.
• Children with milder DKA recover in 10-20
hr(and need less total IV fluid before
switching to oral intake.)
• Those with more severe DKA require 30-36
hrs with this protocol.
• Blood testing should occur every 1-2 hr for
children with severe DKA and 3-4 hr for those
with mild to moderate DKA.
71. INSULIN THERAPY
Timing-1-2 hr after starting fluid replacement.
Type-Only IV Regular insulin used for m/m of DKA.
Dose-low dose iv insulin 0.1 u/kg/hr is standard.high
dose has risk of hypoglycemia,hypokalemia and
rapid decline in osmolality.
Prepration-50 units diluted in 50 ml NS to arrive
conc. Of 1 u/ml
Duration-administered at same rate(0.1u/kg/hr) until
resolution of DKA
Dose adjustment-If hypoglycemia occurs despite
increase in strength of dextrose sol. the dose of
insulin reduced in decrement of 0.02u/kg/hr upto
0.05 u/kg /hr
72. Transition to subcutaneous insulin
therapy
• As oral feeds advanced iv fluids reduced and
change to subcutaneous insulin planned.
• Timing-ideal time to begin is just before a meal.
• Rapid acting insulin(lispro,aspart) are
administered sc 15-30 mins prior and regular
insulin 1-2 hr prior to stopping infusion to avois
rebound hyperglycemia.
• Dose-For pt with DKA at ds onset,recommended
TDD is 0.75-1 u/kg(pre pubertal) and 1-1.2
u/kg(pubertal).
• Before Breakfast-2/3 tdd(1/3 r.a. and 2/3 i.a.
insulin)
73. Cerebral Edema.
Management
•Head end elevation
•Give Mannitol 0.5-1 gm/kg and repeat if there is
no response in 30 mins-2hrs
•3% Hypertonic saline (5 ml/kg over 30 mins) can
be given
•Restrict iv fluids to 2/3
•Replace deficit in 72 hr rather than 48 hr
•Intubation and ventilation if required
Notas do Editor
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Due to b-cell reserve optimal function & initiation of insulin therapy.
Leads to normal blood glucose level without exogenous insulin.
Observed in 50-60% of newly diagnosed patients & it can last up to one year but it always ends.
Can confuse patients & parents if not educated about it early
Insulin associated antibodies (IAA) are usually the 1st to appear in young children, followed by glutamic acid decarboxylase 65 kd (GAD65) and tyrosine phosphatase insulinoma-associated 2 (IA-2) antibodies. The earliest antibodies are predominantly of the IgG1 subclass
Between 3 and 8 a.m., your body starts to increase the amounts of counter-regulatory hormones (growth hormone, cortisol, and catecholamines). These hormones work against insulin&apos;s action to drop blood sugars
It is also called &quot;rebound hyperglycemia
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Adjuvant treatment that suppress autoimmunity include:
Insulin
C-peptide
IGF1