DIABETES MELLITUS TYPE 1 & MANAGEMENT OF DIABETIC KETOACIDOSIS

DIABETES MELLITUS TYPE 1 & MANAGEMENT OF DIABETIC KETOACIDOSIS

1. DIABETES MELLITUS DIABETES MELLITUS
TYPE 1 & TYPE 1 &
MANAGEMENT OF MANAGEMENT OF
DIABETIC DIABETIC
KETOACIDOSIS KETOACIDOSIS
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 b-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

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.

20. CLINICAL
PRESENTATIONS
Classical symptom triad:
polyuria, polydipsia and weight loss
DKA
Accidental diagnosis
Anorexia nervosa like illness

21. DIAGNOSTIC CRITERIA
Fasting blood glucose
level
Diabetic
Plasma >7.0 mmol/
126mg/dl
Capillary >6.0 mmol
IGT
Plasma 6.0-6.9 mmol
Capillary 5.6-6.0 mmol
2 hours after glucose
load
(Plasma or capillary BS)
IGT
7.8-11.0
Diabetic level
> 11.1 (200 mg)

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.

23. COMPLICATIONS OF
DIABETES
Acute:
DKA
Hypoglycemia
Late-onset:
Retinopathy
Neuropathy
Nephropathy
Ischemic heart disease & stroke

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 b-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.

33. Intermediate-acting
Insulin
Examples:NPH, Lente
Onset: Reaches the blood stream about
2 to 4 hours after injection.
Peaktime: Peaks 4-12 hours later.
Duration: Effective for about 12 to 18
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

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.

40. ADVERSE EFFECTS OF
INSULIN
Hypoglycemia
Lipoatrophy
Lipohypertrophy
Obesity
Insulin allergy
Insulin antibodies
Insulin induced edema

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.

54. PREDICTION OF
DIABETES
Sensitive & specific immunologic
markers
GAD Antibodies
GLIMA antibodies
IA-2 antibodies
Sensitive genetic markers
•HLA haplotypes
•DQ molecular markers

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

56. .

MANAGEMENT OF
DIABETIC KETOACIDOSIS

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

60. .
EXAMINATION
Fruity odour in breath
Tachycardia
Low volume pulses
Hypotension
Impaired skin turgor
Delayed capillary refill time
Dehydration
Rapid,Deep sighing respiration Kussumaul
respiration(met. Acidosis)
Bradycardia,hypertension,pappiloedema
Abnormal pupillary reflex,cranial n. palsy
posturing

61. .
Biochemical signs
•Ketones in urine
•Elevated blood glucose(>200 mg%)
•Acidemia(pH<7.3)
•Collect blood for RFT , CBC, SGOT, SGPT,
BloodC/S (if evidence of infection)

62. .
Confirm diagnosis of Diabetic
Ketoacidosis

63. .
Mild:pH<7.3, bicarbonate<15mmol/lit
Moderate :pH<7.2, bicarbonate<10
mmol/lit
Severe:pH<7.1,bicarbonate<5 mmol/lit

64. .
Shock
Reduced
peripheral Pulse
volume
Reduced concious
Dehdration>5%
Not in shock
Clinically
acidotic
Vomitiing
Dehydration <5%
clinically

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.
1
ST
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,neurological
status.Usefloe sheet. Have Mannitol at
bedside;1 g/kg IV push for cerebral
edema
2
nd
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 oral
K solution OR increase IV K to 80 mEq/L
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 1
st
24
hr and is sutracted before calculating the
IV rate.
•Sample calculation for a 30 kg child:
•1
st
hr=300ml IV bolus 0.9%NaCl or LR
•2
nd
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)
•Before dinner-1/3 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