DIABETES MELLITUS

TYPE 1 &
MANAGEMENT OF
DIABETIC
KETOACIDOSIS
PRESENTED BY
DR ASHISH SHARMA
GUIDED BY
DR MEENA PATEL

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.

OLD CLASSIFICATION
(1985)
Type 1, Insulin-dependent (IDDM)
Type 2, Non Insulin-dependent (NIDDM)
obese
non-obese
MODY
IGT
Gestational Diabetes

WHO CLASSIFICATION
2000
Is based on etiology not on type of
treatment or age of the patient.
Type 1 Diabetes
(idiopathic or autoimmune -cell
destruction)

Type 2 Diabetes
(defects in insulin secretion or action)

Other specific types

 Both type 1 & type 2 can be further

subdivided into:
Not insulin requiring
Insulin requiring for control
Insulin requiring for survival

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

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.

Pathogenesis &
Natural history
The natural history includes
distinct stages
1) Initiation of autoimmunity
2)Preclinical autoimmunity with progressive
loss of -cell function
3)Onset of clinical disease
4)Transient remission( Honeymoon period)
5)Established disease
6)Development of complications

Both genetic ,environmental and autoimmune

factors contribute to the pathogenesis.
Genetic factorsGenetic 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

 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%.

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

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

. The earliest antibodies are predominantly

of the IgG1 subclass
The appearance of autoimmunity is followed
by progressive destruction of cells.
Antibodies are a marker for the presence of
autoimmunity, but the actual damage to the
cells is primarily T-cell mediated

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

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.

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)

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.

CLINICAL
PRESENTATIONS
Classical symptom triad:
polyuria, polydipsia and weight

loss

DKA
Accidental diagnosis
Anorexia nervosa like illness

DIAGNOSTIC CRITERIA
Fasting blood
glucose level
Diabetic
Plasma >7.0 mmol/

2 hours after
glucose load
(Plasma or capillary BS)

IGT

126mg/dl
7.8-11.0
Capillary >6.0 mmol
Diabetic level
IGT
> 11.1 (200 mg)
Plasma 6.0-6.9 mmol
Capillary 5.6-6.0 mmol

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.

COMPLICATIONS OF
DIABETES
Acute:
DKA
Hypoglycemia

Late-onset:
Retinopathy
Neuropathy
Nephropathy
Ischemic heart disease & stroke

TREATMENT GOALS
Prevent death & alleviate symptoms
Achieve biochemical control
Maintain growth & development
Prevent acute complications
Prevent or delay late-onset
complications

TREATMENT ELEMENTS
Education
Insulin therapy
Diet and meal planning
Monitoring
HbA1c every 2-months
Home regular BG monitoring
Home urine ketones tests when

indicated

EDUCATION
Educate child & care givers
about:
Diabetes
Insulin
Life-saving skills
Recognition of Hypo & DKA
Meal plan
Sick-day management

INSULIN
A polypeptide made of 2 -chains.
Discovered by Bants & Best in 1921.
Animal types (porcine & bovine) were
used before the introduction of humanlike insulin (DNA-recombinant types).
Recently more potent insulin analogs
are produced by changing aminoacid
sequence.

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.

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.

The Basics of Insulin:

4 Types
Rapid-acting insulin
Regular or short-acting insulin
Intermediate-acting insulin
Long-acting insulin

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

Regular or Shortacting Insulin

Examples: insulin lispro, Aspart
Onset: Reaches the bloodstream
within 30 minutes after injection.
Peaktime: Peaks anywhere from 23 hours after injection.
Duration: Effective for
approximately 3-6 hours.

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

Long-acting Insulin
Examples: insulin glargine
Onset:
Reaches the bloodstream
6-10 hours after injection
Duration: Usually effective for 2024 hours

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.

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

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.

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.

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

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

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.

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.

MONITORING
Compliance (check records)
HBG tests
HbA1 every 2 months
Insulin & meal plan
Growth & development
Well being & life style
School & hobbies

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

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.

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

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.

PITFALLS OF
MANAGEMENT
Delayed diagnosis of IDDM
The honey-moon period
Detection & treatment of NIDDY
Problems with diagnosis &
treatment of DKA & hypoglycemia
Somogyis effect & dawn
phenomenon may go unrecognized.

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.

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.

IMMUNE MODULATION
Immunosuppressive therapy for
Newly diagnosed
Prolonged the honey moon
For high risk children
Immune modulating drugs
Nicotinamide
mycophenolate

GENE THERAPY
Blocks the immunologic attack
against islet-cells by DNAplasmids encoding self antigen.
Gene encode cytokine inhibitors.
Modifying gene expressed isletcell antigens like GAD.

PREDICTION OF
DIABETES
Sensitive & specific immunologic
markers
GAD Antibodies
GLIMA antibodies
IA-2 antibodies

Sensitive genetic markers

HLA haplotypes
DQ molecular markers

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

.
MANAGEMENT OF
DIABETIC KETOACIDOSIS

 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

 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

 CLINICAL HISTORY
.
Polyuria
Polydipsia
Weight loss
Nausea,vomiting,abdominal pain
Headache
Restlessness,irritability
Lethargy,altered sensorium,loss of
conciousness
Fever

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,pappiloedem
a
Abnormal pupillary reflex,cranial n.
palsy
posturing

.
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)

Confirm diagnosis of
Diabetic Ketoacidosis

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

.
Shock
Reduced
peripheral Pulse
volume
Reduced concious

Dehdration>5%
Not in shock
Clinically
acidotic
Vomitiing

Dehydration <5%
clinically

Resuscitation
Airway+NG tube
Circulation(10-20ml/kg of
0.9% NS over 30-60
mins)
Repeat if necessaryinitial 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 34hrly

No
improvement

.
No
improveme
nt

Reevaluate
Uncorrected
hypovolemia
Review dose
and rate of
insulin
infusion

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

Neurologica
l
deterioration
warning
signs
Headache
Irritability
Slowing heart
rate
Reduced
conciousness
level
Hypertension
Bradycardia
Pupillary
inequality

Consider
Cerebral
Edema(Exclu
de
Hypoglycemi
a)

.
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,

Insulin
Start
subcutaneiu
s insulin and
then stop iv
insulin
infusion 1 hr
later

Improvement
No emesis
Normal
electrolytes
CO2 >16mEq/L
pH>7.3

DIABETIC KETOACIDOSIS
TREATMENT PROTOCOL.
TIME

THERAPY

COMMENTS

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 b

repeated.NPO.Monitor
I/O,neurological status.Usefloe
sheet. Have Mannitol at
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/23h

Oral intake with

subcutaneous insulin

No emesis;CO2> 16
mEq/L;normal electrolytes

Variable

If K<3mEq/L,give 0.5 to 1
mEq/kg as oral K solution OR
increase IV K to 80 mEq/L

 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)

 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.

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

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)

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