This document discusses Diabetes Mellitus Type 1 and the management of Diabetic Ketoacidosis (DKA). It begins with a case scenario of a 5-year-old boy brought to the emergency department with abdominal pain, diarrhea, increased urination and vomiting who was found to have DKA. The document then provides background on diabetes, including the classification of diabetes types, pathophysiology, diagnosis, genetics, environmental factors, clinical manifestations, treatment including insulin therapy, and goals of treatment.

1. D R A N K I T G U P T A , M D
K I M S , K A R A D
DIABETES MELLITUS 1 and
MANAGEMENT OF DIABETIC
KETOACIDOSIS

2. CASE SCENARIO
 A 5 year old male child was brought to the
emergency department with complaints of acute pain
in abdomen with acute diarrhea, increased urination
and vomiting. Child was severely dehydrated. Child
was given IV fluid boluses, investigations sent and
child sent for emergency abdominal USG. Child
succumbed
 Pitfalls ?
 It was a case of Diabetic ketoacidosis
 Sugar was not taken on admission
 Management wrong

3. FACE OF DIABETES IN 1920

4. 1923
Banting and Best Awarded
Nobel Prize for Discovery
And Use of Insulin in the
Treatment of IDDM

5. INTRODUCTION
 The term diabetes mellitus describes a 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
 Factors contributing to hyperglycemia include decreased
insulin secretion, decreased insulin action and increased
glucose production
 Hyperglycemia leads to multi organ damage
 It is the leading cause of end stage renal disease, non-
traumatic leg amputation and adult blindness

6. GOALS AND OBJECTIVES
 Understand the action of insulin on the metabolism of
carbohydrates, protein & fat
 Understand the pathophysiology of DM1 & DKA
 Understand the management approach to the patient with
DKA
 Appreciate the complications that occur during treatment

7. OLD CLASSIFICATION
 Type 1, Insulin-dependent (IDDM)
 Type 2, Non Insulin-dependent (NIDDM)
 Obese
 non-obese
 MODY
 Impaired glucose tolerance
 Gestational Diabetes

8. CLASSIFICATION
 Type I (insulin-dependent diabetes mellitus, IDDM)
 Severe lacking of insulin, dependent on exogenous insulin
 DKA
 Onset in childhood
 ?genetic disposition & is likely auto-immune-mediated
 Type II (non-insulin-dependent diabetes mellitus, NIDDM)
 Not insulin dependent, no ketosis
 Older patient (>40), high incidence of obesity
 Insulin resistant
 No genetic disposition
 Increase incidence due to prevalence of childhood obesity

9. EPIDEMIOLOGY
 1.9/1000 among school-age children in the US
 Indian data suggest an incidence of 10.5/100,000
 India would have 79 million diabetics by 2030, the
highest for any country in the world
 Equal male to female
 Peaks age 5-7 yrs and adolescence
 Newly recognized cases: more in autumn & winter
 Increase incidence in children with congenital rubella
syndrome, Turner and Down’s syndrome

10. TYPE 1 DM
 15-70% of children with Type I DM present in DKA at
disease onset
 1/350 of type I DM will experience DKA by age 18 yr
 Risk of DKA increased by:
 Very young children
 Lower socioeconomic background
 No family history of Type I DM
 DKA:
 Most frequent cause of death in Type I DM
 One of the most common reasons for admission to PICU

11. NATURAL HISTORY
 4 DISTINCT STAGES
 Pre clinical beta cell autoimmunity with progressive defect of
insulin secretion
 Onset of clinical diabetes
 Transient remission ‘honeymoon period’
 Established diabetes during which there may occur acute or
chronic complications and decreased life expectancy

12. TYPE OF DIABETES IN CHILDREN
 Type 1 diabetes mellitus accounts for >90% of cases.
 Type 2 diabetes is increasingly recognized in children with
presentation like in adults.
 Permanent neonatal diabetes
 Transient neonatal diabetes
 Maturity-onset diabetes of the young
 Secondary diabetes e.g. in cystic fibrosis or Cushing
syndrome

13. TYPE 2 DM
 Most prevalent form of diabetes in adults, which is
characterized by insulin resistance and often a
progressive defect in insulin secretion
 Presentation is insidious
 The incidence has increased in children by more
than 10 fold, depending on geography and as a result
of the epidemic of childhood obesity

14. DIFFERENCE
FEATURES TYPE1DM TYPE2DM
Onset Rapid Slow
Age of onset Before 30 years After 30 years
Obesity Thin, weight loss Overweight
HLA association Significant No
Family history 10% +++
Microvascular
complications
100% Many years after
diagnosis
Islet cell autoimmunity Frequent Absent

15. TRANSIENT NEONATAL DIABETES
 Observed in both term & preterm babies, but more
common in preterm
 Caused by immaturity of islet b-cells
 Polyuria & dehydration are prominent, but baby
looks well & suck vigorously
 Highly sensitive to insulin
 Disappears in 4-6 weeks

16. PERMANENT NEONATAL DIABETES
 A familial form of diabetes that appear shortly after
birth & continue for life
 The usual genetic & immunologic markers of Type 1
diabetes are absent
 Insulin requiring, but ketosis resistant
 Is often associated with other congenital anomalies
& syndromes e.g. Wolcott-Rallison syndrome.

17. MODY
 Usually affects older children & adolescents
 Not rare as previously considered
 Also referred to as monogenic diabetes
 5 subclasses are identified, one subclass has specific
mode of inheritance (AD)
 No immunologic destruction of beta cells and no
HLA association
 Not associated with immunologic or genetic markers
 Insulin resistance is present

18. IMPAIRED GLUCOSE TOLERANCE
 A metabolic stage that is intermediate between
normal glucose homeostasis and diabetes
 A fasting glucose concentration of 99mg/dl is the
upper limit of normal
 In the absence of pregnancy, IGT is not a clinical
entity but rather a risk factor for future diabetes and
cardiovascular disease
 IGT is often associated with Insulin resistance
syndrome

19. INSULIN RESISTANCE SYNDROME
 It consists of
 Insulin resistance
 Compensatory hyperinsulinemia
 Obesity
 Dyslipidemia
 Hypertension
 Insulin resistance is directly involved in the
pathology of type 2 DM

20. DIAGNOSTIC CRITERIA
IMPAIRED GLUCOSE TOLERANCE DIABETES MELLITUS
Fasting glucose 100-125 mg/dl Symptoms of Diabetes mellitus plus
random plasma glucose ≥200 mg/dl
2 hour plasma glucose during the OGTT
≥140mg/dl but <200mg/dl
Fasting (at least 8 hour) plasma
glucose ≥126mg/dl
2 hour plasma glucose during OGTT
≥200mg/dl
Hemoglobin A1c ≥6.5%
Symptoms include polyuria, polydipsia, and unexplained weight loss with
glucosuria and ketonuria
OGTT – Oral glucose tolerance test

21. GENETICS
 Clear familial clustering of T1DM, with prevalence in
siblings approaching 6% as opposed to 0.4% in general
population
 Risk is increased when a parent has diabetes
 3-4% if mother have
 5-6% if father have
 Twins
 Monozygotic – 30-65%
 Dizygotic – 6-10%
 85% of newly diagnosed patients do not have a family
member with diabetes
 So we cannot rely on family history completely

22. GENES ALTERING THE RISK
 Genetic region with the greatest contribution to the
risk of T1DM is the major histocompatibilty complex
on chromosome 6
 Region with next highest ratio is the promoter region
5 of the insulin gene on chromosome 11
 More than 50 other risk loci have been identified
 Some are
 Insulin
 PTPN22, PTPN2, CD25, CTLA4, IFIH1

23. MAJOR HISTOCOMPATIBILITY COMPLEX
 It is large genomic region that contains a number of
genes related to immune system function in humans
 Further divided into class 1,2,3 and 4 genes
 Class 2 is most strongly associated
 Some of the known associations include HLA DR3/DR4-
DQ2/8
 Comparison of risk
 Normal population - 1 in 300
 With DR3/4-DQ2/8 gene – 1 in 20
 Risk increases more when HLA is shared with a sibling or
a parent

24. OTHER FACTORS
 Aspartate at position 57 in DQB1
 Human leukocyte antigen class 1
 Insulin gene locus, IDDM2
 PTPN22
 Cytotoxic T lymphocyte antigen 4
 Interleukin -2 receptor

25. ENVIRONMENTAL FACTORS
 Evidence that environment plays a significant role is
provided by
 Variation seen in urban and rural areas populated by the same
ethnic group
 Increase in incidence in all populations in the last decade
 Occurrence of seasonality
 Change in incidence that occur with migration

26.  VIRAL INFECTIONS
 No single virus stands out in the etiology
 Variety of viruses and mechanisms may contribute to the
development
 Mechanisms may be
 Direct infection of beta cells by viruses resulting in lysis and
release of self antigens
 Molecular mimicry
 ENTEROVIRUSES
 Increase in evidence of enteroviral infection in patients with
T1DM and an increased prevalence of enteroviral RNA in
prenatal samples from children who subsequently develop
T1DM

27.  CONGENITAL RUBELLA SYNDROME
 Prenatal infection with rubella is associated with beta cell
autoimmunity in up to 70%
 Development of T1DM in up to 40%
 Time lag may be as high as 20 years
 No increase in risk when rubella infection occurs after birth
 MUMPS VIRUS
 May lead to development of beta cell autoimmunity with high
frequency and to T1DM in some cases

28. HYGIENE HYPOTHESIS
 Infectious agents may play a role in protection
 It states that lack of exposure to childhood infections
may increase an individual’s chances of developing
autoimmune diseases, including T1DM
 Rate of T1DM and other autoimmune disorders are
generally lower in underdeveloped nations with a
high prevalence of childhood infections
 These tend to increase as these countries become more
developed

29. DIET
 Breastfeeding may lower the risk directly or
indirectly by delaying exposure to cow’s milk protein
 Early introduction of cow milk and gluten are
implicated in the development of autoimmunity
 Implicated antigens include beta lactglobulin
 Other dietary factors that have been suggested are
 Omega 3 fatty acids
 Vitamin D
 Ascorbic acid, Zinc and Vit E

30. PATHOGENESIS
 Natural history of T1DM involves some or all of the
following stages
 Initiation of autoimmunity
 Preclinical autoimmunity with progressive loss of beta cell
function
 Onset of clinical disease
 Transient remission
 Established disease
 Development of complications

31. AUTOIMMUNE FACTORS AND AUTOIMMUNITY
 Individuals susceptible to develop diabetes have
normal beta cell mass at birth
 Autoimmune destruction affects only the beta cells of
the islets even though the alpha and delta cells are
functionally and embryologically similar
 A genetic susceptible host develops autoimmunity
against host’s own cells
 What triggers this autoimmune response remains
unclear at this time

32.  Whatever the triggering factor, it seems that in most
cases that are diagnosed in childhood, onset of
autoimmunity occurs very early in life
 Development of autoimmunity is associated with
appearance of auto antibodies
 In some but not all it is followed by progressive
destruction of beta cells
 Antibodies are marker for the presence of
autoimmunity but the actual damage is primarily T-
cell mediated

33. PROGRESSIVE LOSS OF BETA CELL FUNCTION
 Histologic analysis of the pancreas from patients
with recent onset T1DM reveals insultits
 Infiltration of islets of langerhans by mononuclear
cells, including T and B lymphocytes, monocytes and
natural killer cells occurs
 At the time of diagnosis some viable beta cells are
still present and these may produce enough insulin
to lead to a partial remission of the disease
(honeymoon period)

35.  But over time, almost all beta cells are destroyed and
patient become totally dependent on exogenous
insulin for survival
 Clinical diabetes occurs when pancreas loses 80% or
more of its insulin secretary ability
 Over time some of these patients develop secondary
complications of diabetes that appear to be related to
how well-controlled the diabetes has been

36. PREDICTION AND PREVENTION
 Autoimmunity precedes clinical T1DM
 Individuals at risk may be identified by a
combination of genetic, immunologic and metabolic
markers
 In 1st degree relatives
 Number of positive auto antibodies can help estimate the risk
 Single auto antibodies – 2-6%
 2 auto antibodies – 21-40%
 >2 auto antibodies – 59-80%

37. PREVENTION
 PRIMARY PREVENTION
 Delaying the introduction of cow milk’s protein, delaying
introduction of cereals and increasing duration of
breastfeeding
 Oral insulin may delay the incidence of diabetes in only some
of auto-antibody positive but still prediabetic patients
 SECONDARY PREVENTION
 Immunosuppressants like cyclosporine may prolong the
honeymoon period but are associated with side effects
 Glucagon like peptide -1 agonists alone or in combination with
immunomedulatory therapies can increase beta cell mass and
are being explored

38. CLINICAL MANIFESTATIONS
 Initially when insulin reserve is limited postprandial
hyperglycemia occurs
 When the serum glucose increase above the renal
threshold, intermittent polyuria or nocturia begins
 When extremely low insulin levels are reached,
ketoacids accumulates
 Child may have polydypsia, weight loss, polyphagia
and fatigue

39. DIAGNOSIS
 ONCE HYPERGLYCEMIA IS CONFIRMED
 It is to determine whether DKA is present and to
evaluate electrolyte abnormalities
 A baseline hemoglobin A1c will be confirmatory
 Also allows an estimate of the duration of hyperglycemia
 Provides an initial value to compare the effectiveness of
therapy

40. COURSE OF ILLNESS
 Most children respond to insulin
 Once insulin is initiated sugars gradually decline
 Often after around a week, need for exogenous
insulin declines due to tansient recovery of insulin
secretion
 This phase is called ‘honeymoon phase of diabetes’
 It lasts for some days to months
 Insulin needs increase over time till when pancreas
no longer secrete insulin
 At this point req plateaus at 0.8-1 unit/kg/day

41. TREATMENT
 GOALS OF THERAPY
 Eliminate symptoms related to hyperglycemia
 Reduce and delay the complications
 Achieve a normal lifestyle and normal emotional and social
development
 Achieve normal physical growth and development
 Detect associated diseases early

42. INSULIN THERAPY
 LIMITATIONS
 Exogenous insulin does not have to pass to the liver
 Absorption continues despite hypoglycemia
 Absorption rate varies by injection site and patient activity
level
 Despite these fundamental physiologic differences,
acceptable glucose control can be obtained with
insulin analogs used in a basal bolus regimen
 Slow onset, long duration for between meal glucose
 Rapid onset for each meal

43. INSULIN PREPERATIONS
PREPERATIONS PROPERTIES ONSET EFFECTIVE
DURATION
SHORT ACTING
LISPRO
INSULIN ASPART
REGULAR
Faster onset
Faster onset
15 min
15 min
30 min
3-4 hr
3-6 hr
3-6 hr
INTERMEDIATE
NPH INSULIN
LENTE
Slower onset
Longer duration
2-4 hour
3-4 hour
10-16 hour
12-18 hour
LONG ACTING
ULTRA LENTE
GLARGINE
Slower duration
Longer duration
6-10 hour
4 hour
18-20 hour
24 hour

44. INSULIN PREPERATIONS
 Current insulin preparations are generated using
recombinant DNA technology
 Animal insulins should be avoided
 Lispro allows better control of sugar as its action is
faster and duration longer than regular insulin
 All preanalog insulins form hexamers, which must
dissociate into monomers subcutaneously before
being absorbed into the circulation

45. INSULIN PRESCRIPTION
 Insulin req range from 0.5-1 unit/kg/day
 Goal of therapy is to
 Provide background insulin to maintain glycemic control
during the fasting state
 Punctuate this with multiple boluses of short acting insulins to
maintain euglycemia during post-prandial state
 In most traditional regimens
 Intermediate or long acting insulin is utilized to provide
background insulin to maintain glycemic control during
fasting state
 Short acting insulins in the postprandial state

46. INSULIN REGIMEN
 NPH REGIMEN
 Combination of NPH and short acting insulin before breakfast
 Short acting preparation at dinner
 NPH at dinner or bedtime
 When drawing up the mixed dose
 Short acting insulin is drawn before intermediate acting insulin as
accidental introduction of longer acting insulin in short acting
insulin can result in increased duration of effect
 A meal is planned incorporating 3 meals and 2-3 snacks

47.  GLRAGINE REGIMEN
 Multiple daily injections of Lispro or Aspart with baseline
insulin levels achieved using Glargine insulin
 Glargine is given once daily either in morning or evening
 Short acting is given with every meal and snack
 Dose of short acting insulin is calculated based on
carbohydrate ratio
 1 unit of insulin per 20-30gm of carbohydrates in young children
 1 unit/10-15 gm in older children
 1 unit/5 gm in adults

48. MONITORING
 Insulin is adjusted by reviewing blood sugars
 Blood sugars are monitored at least four times/day
 Variation in meal amounts and timing can result in
wide fluctuations in blood sugars
 Variation in physical activity and exercise will also
affect the insulin/blood sugar dynamics

49. INSULIN PUMPS
 These are being increasingly used in the western
world
 Principle involved is the refined glargine regimen
 Advantages are
 Ability to vary the basal insulin during the day and night
 Usefulness in preventing early morning hyperglycemia
secondary to Dawn phenomenon
 Allowing alteration of basal rates during exercise
 Allowing boluses to be given in different wave forms

51. COMPLICATIONS
 ACUTE
 Diabetic Ketoacidosis
 Hypoglycemia
 INTERMEDIATE
 Lipoatrophy
 Limited joint mobility
 Growth failure
 Delay in sexual maturation
 CHRONIC
 Retinopathy
 Neuropathy
 Nephropathy

52. HYPOGLYCEMIA
 When child is been unusually active and insulin/food
is not adjusted accordingly
 Adrenergic symptoms such as tremors, pallor,
tachycardia and sweating can be seen
 Treatment follows a rule of 15
 15gm of free sugar are given in the form of sugar, honey or
juice followed by recheck of blood sugar in 15 min
 if child is unconscious glucagon IM should be given
 Dose is 0.3 mg for infants, 0.5 mg < 25 kg and 1 mg >
25 kg

53. LIPOATROPHY

54. NEPHROPATHY
 Diabetes #1 cause of end-stage renal disease (ESRD)
 1st manifestation = microalbuminuria (low but abnormal,
30 mg/day or 20 µg/min urine albumin)
 Without intervention
 In 80% albumin excretion increases 10–20% / year to overt
nephropathy (albumin = 300 mg/24 h or 200 µg/min) over 10–15
yr
 Once nephropathy occurs
 GFR falls over several years (2–20 ml · min-1 · year-1).
 ESRD develops
 in 50% of type 1 DM with nephropathy within 10 years
 and in 75% by 20 yr.
 Microalbuminuria is rare with short duration of type 1 DM
 Screening in type 1 DM should begin after 5 yr of disease

55. RETINOPATHY
 After 20 yr, nearly all patients with T1 DM and
>60% with T2 DM have some retinopathy
 In patients with T1 DM
 3.6% of young-onset patients (aged <30 yr at dx) were
legally blind
 86% of blindness was due to diabetic retinopathy
 1.6% of old-onset patients (aged 30 yr at dx) were legally
blind.
 Vision-threatening retinopathy almost never
occurs with T1 DM in the first 3–5 years of
diabetes or before puberty.

56. DAWN AND SOMOGYI PHENOMENON
 Dawn phenomenon
 Leads to increased blood glucose levels in early morning
 Due to overnight growth hormone secretion and increased
insulin clearance
 Normal physiologic process but diabetics cannot compensate
 Somogyi phenomenon
 High morning glucose due to rebound from late night or early
morning hypoglycemia

57. DIABETIC KETOACIDOSIS
 Most severe complication of diabetes mellitus
 State of hyperglycemic dehydration and ketotic
acidemia
 Triad of
 Hyperglycemia, acidosis and ketosis
 Blood sugar is typically above 250mg/dl, ketonemia
is present (positive at greater than 1:2 dilution),
serum pH<7.3 and serum bicarbonate <15mEq/l
 Moderate DKA – pH<7.2 and HCO3 <10mEq/l
 Severe DKA – pH<7.1 and HCO3 5mEq/l

58. PRESENTATION
 Can occur as the initial presentation of type 1 DM
 15-70% of newly diagnosed case present as DKA
 Prevalence is 36% in children < 5yr to 16% in >14yr
 Cerebral oedema accounts for most of the DKA
related deaths
 Causes
 Undiagnosed cases
 Non compliance to insulin therapy
 Failure of insulin pumps
 Infections

59. HYPERGLYCEMIC HYPEROSMOLAR STATE
 It is characterized by severe hyperglycemia (usually
> 600mg/dl), hyperosmolality (>350 mOsm/kg),
low plasma ketones and dehydration
 Usually a complication of type 2 DM
 Can occur in type 1 DM if insulin is present to
prevent ketoacidosis but is insufficient to control the
blood sugar

60. PATHOPHYSIOLOGY
 MOST IMPORTANT CONTRIBUTING FACTOR IS
INSULIN DEFICIENCY
 Coupled with increase in counter regulatory hormones like
glucagon, growth hormone and cortisol
 Results in increased glucose production from glycogenolysis
and gluconeogenesis while limiting glucose utilization
 Results in hyperglycemia and lipolysis resulting in
increased fatty acid production
 Oxidation of fatty acids in liver generate beta hydroxybutyrate
and acetoacetic acid (acetone)
 Results in acidosis and ketosis

61.  Hyperglycemia leads to osmotic diuresis
 Causing dehydration and hypovolemia
 Acidosis causes shift of intracellular ions to
extracellular
 Especially potassium which may be high even when total body
potassium is low
 Ketosis and acidosis leads to
 Fruity odor and rapid respirations (Kussmaul breathing)
 Hypertriglyceridemia and hyperglycemia
 Falsely lower the serum sodium resulting in
pseudohyponatremia

62. CLINICAL FEATURES
SYPMTOMS PHYSICAL FINDINGS
Abdominal pain Tachycardia
Nausea and vomiting Dehydration , hypotension
Polyuria and diarrhea Tachypnea, kussmaul respiration
Shortness of breath Abdominal tenderness
Polydipsia Lethargy, cerebral edema and coma
Fever Signs of infection

63. LABORATORY EVALUATION
 Blood glucose > 250 mg/dl, blood pH < 7.3 and
HCO3 < 15 mEq/l
 Normal or high potassium
 Low sodium
 Leukocytosis and hypertriglyceridemia
 Raised serum ketones and urinary ketones

64. MANAGEMENT
 GOALS OF MANAGEMENT
 Slow correction of dehydration and acidosis
 Correction of electrolyte imbalance
 Prevent the development of cerebral edema

65. FLUIDS AND ELECTROLYTES
 INITIAL FLUID BASED ON BLOOD PRESSURE
 Administer 10-20 ml/kg normal saline over 1 hour
 No boluses
 If hypovolemia persists repeat NS for next hour
 Calculate fluid deficit based on 10% dehydration
 Not to exceed 4l/sqm/day
 Infuse 0.45% saline until blood sugar is >300mg/dl
 Potassium is added once urine flow is established
and serum K <5.5 mEq/l

66. USE OF BICARBONATE
 NO, NO AND NO
 Is to be avoided as much as possible
 Bicarb administration leads to increased cerebral acidosis:
 HCO3
- + H+  dissociated to CO2 and H2O
 Bicarbonate passes the BBB slowly
 CO2 diffuses freely  exacerbating cerebral acidosis & depression
 May be used cautiously if pH does not improve and
arterial pH remains <7.0 and HCO3 <5 mEq/l
 Discontinue when pH>7.1 and HCO3 > 10 mEq/l

67. INSULIN THERAPY
 Following initial hydration, start insulin drip at 0.1
units/kg/hour
 If already received insulin start with half dose
 When glucose <300mg/dl
 Change IV fluids to 5% dextrose with 0.45% saline
 When glucose <180mg/dl
 Change IV fluids to 10% dextrose with 0.45% saline
 When glucose <150mg/dl
 Reduce insulin at 0.02units/kg/hour

68.  Rate of fall of glucose should be 80-100 mg/dl/hr
 If there is no fall in plasma glucose in 2-3 hours
 Increase insulin infusion to 0.15 u/kg/hr
 Do not discontinue insulin infusion until after
subcutaneous insulin has been given
 Insulin must be continued until pH > 7.36 or HCO3
> 20 mEq/l

69. MONITORING
 Vital signs every hour
 Fluid balance, intake and output monitoring
 Blood sugar, electrolytes, pH, HCO3
 Initially 1-2 hour, then every 4 hour
 Calcium, phosphate, and magnesium every 12 hour
 Screen for infections

70. CEREBRAL EDEMA
 Cerebral edema: 0.5-1% of pediatric DKA
 Mortality rate of 20%
 Responsible for 50-60% of diabetes deaths in children
 Permanent neurologic disability rate of 25%
 Typically develops within the first 24 hrs of treatment
 Etiology is still unclear
 Signs & symptoms:
 Headache
 Confusion
 Slurred speech
 Bradycardia
 Hypertension

71. PATHOPHYSIOLOGY
 Theories of cerebral edema
 Rapid decline in serum osmolality
 This leads to the recommendation of limiting the rate of fluid
administration
 Edema due to cerebral hypoperfusion or hypoxia
 Activation of ion transporters in the brain
 Direct effects of ketoacidosis and/or cytokines on endothelial
function

72. RISK FACTORS
 Younger age
 New onset
 Longer duration of symptoms
 Lower PCO2
 Severe acidosis
•Increase in BUN
•Use of bicarbonate
•Large volumes of
rehydration fluids
•Failure of correction of
Na with treatment

73. TREATMENT
 RATE OF FLUID ADMISNISTERATION TO BE
REDUCED AND STOP BICARBONATE IF GIVING
 Lower intracranial pressure
 Mannitol or 3% saline
 Imaging to rule out other pathologies
 Hyperventilation & surgical decompression are less
successful at preventing neurologic morbidity & mortality

74. SPECIFIC RECOMMENDATIONS
 A visit to specialist every 3 months interval
 Assessment of growth, weight and puberty
 Physical examination
 Assessment of blood sugar records
 Eye examination annually
 Glycated Hb every 3 months
 Fasting serum lipids and thyroid function tests every year
 For a child receiving continuous subcutaneous insulin: specific
education should be reviewed and pump function assessed
 Ongoing diabetes education is necessary